2019年12月29日 星期日
2019 老年糖尿病 抗糖尿病藥物選擇
2025-03-13 11:06AM
2019-12-30
老年人血糖控制目標
老年糖尿病藥物選擇
1. 80歲以上沒有吃過 metformin 的不建議給 metformin
2. 有乳酸中毒危險因子的不建議用metformin, 包括
~ eGFR < 30
~ 心臟功能不良
~ 低血氧
~ 敗血症急性期
3. 促胰島素分泌藥物, 建議選短效的, 例如 Gliclazide, Glipizide
4. TZD 副作用包括水腫, 骨折, 而 TZD + 胰島素會增加心衰竭風險, 所以不建議用於心衰竭患者
5. DPP4i 會增加UTI和急性胰臟炎風險, Linagliptin(Trajenta) 腎衰竭患者不用減量
6. SGLT2i 會增加UTI機率, 因排糖增加, 也會讓病患體重減輕, 不適合用在太瘦的人
7. 胰島素可能導致體重增加
基礎胰島素與胰島素類似物
第二代基礎胰島素類似物
第二代基礎胰島素效益與安全性之比較
第一代與第二代基礎胰島素類似物 Gla-300 vs IDeg-100 (degludec) vs 之間的比較
GLP1RA 是注射型藥物
1. 不建議與 SU 或 no SU 並用
2. 不建議與胰島素/TZD 併用
剛剛幫一個89歲患者新增抗糖尿病藥物. 年齡>80所以不建議開 metformin.
病患過去不曾下肢水腫. 腎功能 eGFR 45.
先挑了 pioglitazone. 但後來回顧一下這個藥物禁忌. 它會增加骨鬆風險.
後來改選 trajenta (DPP4i)
2019-12-30
老年人血糖控制目標
老年糖尿病藥物選擇
1. 80歲以上沒有吃過 metformin 的不建議給 metformin
2. 有乳酸中毒危險因子的不建議用metformin, 包括
~ eGFR < 30
~ 心臟功能不良
~ 低血氧
~ 敗血症急性期
3. 促胰島素分泌藥物, 建議選短效的, 例如 Gliclazide, Glipizide
4. TZD 副作用包括水腫, 骨折, 而 TZD + 胰島素會增加心衰竭風險, 所以不建議用於心衰竭患者
5. DPP4i 會增加UTI和急性胰臟炎風險, Linagliptin(Trajenta) 腎衰竭患者不用減量
6. SGLT2i 會增加UTI機率, 因排糖增加, 也會讓病患體重減輕, 不適合用在太瘦的人
7. 胰島素可能導致體重增加
基礎胰島素與胰島素類似物
第二代基礎胰島素類似物
第二代基礎胰島素效益與安全性之比較
第一代與第二代基礎胰島素類似物 Gla-300 vs IDeg-100 (degludec) vs 之間的比較
GLP1RA 是注射型藥物
1. 不建議與 SU 或 no SU 並用
2. 不建議與胰島素/TZD 併用
2019 老年糖尿病臨床照護手冊~ 血糖控制目標 A1c
美國糖尿病學會與老年醫學會建議
老 年糖尿病人如具有良好健康狀態與身體功 能，少共病而且可預期壽命仍長，糖化血 色素控制目標建議與一般患者接近，控制於 7.5% 以下。
如身體健康狀態下降又具有多重共病，日常活動功能已有輕中度障 礙，或有輕中度認知障礙，糖化血色素控制目標建議為 8.0% 以下。
至於身體狀態 差，已需要長期機構照護或患有末期慢性 疾病，嚴重認知障礙，建議糖化血色素控制於 8.5% 以下或主要避免高血糖急性症狀即可。 老年糖尿病用藥選擇上，應盡量簡化處 方，並避免發生低血糖。發生低血糖風險高者，建議選用較不易造成低血糖的降血 糖藥物。
老 年糖尿病人如具有良好健康狀態與身體功 能，少共病而且可預期壽命仍長，糖化血 色素控制目標建議與一般患者接近，控制於 7.5% 以下。
如身體健康狀態下降又具有多重共病，日常活動功能已有輕中度障 礙，或有輕中度認知障礙，糖化血色素控制目標建議為 8.0% 以下。
至於身體狀態 差，已需要長期機構照護或患有末期慢性 疾病，嚴重認知障礙，建議糖化血色素控制於 8.5% 以下或主要避免高血糖急性症狀即可。 老年糖尿病用藥選擇上，應盡量簡化處 方，並避免發生低血糖。發生低血糖風險高者，建議選用較不易造成低血糖的降血 糖藥物。
2019 老年糖尿病臨床照護手冊~ 老年糖尿病人血壓控制目標
美國糖尿病學會與老年醫學會建議
老年糖尿病人血壓控制目標應依病患特性做調整，以減少高血壓治療所帶來的副作用。
具有良好功能狀態的健康患者，或身體健康與功能狀態略降低者，血壓控制目標建議為收縮壓控制於 140 mmHg 以下，舒張壓控制於 90 mmHg 以下。
如身體已處於末期慢性病狀態，認知及身體機能中等至嚴重異常之病患，收縮壓可控制於 150 mmHg 以下，舒張壓控制於 90 mmHg 以下。
老年人血壓 血脂肪 血糖控制目標
老年糖尿病人血壓控制目標應依病患特性做調整，以減少高血壓治療所帶來的副作用。
具有良好功能狀態的健康患者，或身體健康與功能狀態略降低者，血壓控制目標建議為收縮壓控制於 140 mmHg 以下，舒張壓控制於 90 mmHg 以下。
如身體已處於末期慢性病狀態，認知及身體機能中等至嚴重異常之病患，收縮壓可控制於 150 mmHg 以下，舒張壓控制於 90 mmHg 以下。
老年人血壓 血脂肪 血糖控制目標
Insulin therapy in type 2 diabetes mellitus TROUBLESHOOTING 2 hypoglycemia
Hypoglycemia — An increased risk of hypoglycemia is a potential complication of insulin therapy. However, patients with type 2 diabetes experience much less frequent hypoglycemia than patients with type 1 diabetes [55].
Although basal insulin is associated with less hypoglycemia than prandial insulin (see 'Insulin initiation' above), hypoglycemia can occur when the dose of basal insulin is titrated to cover meals. If the patient subsequently eats less than usual, hypoglycemia may occur. Alternatively, some patients develop daytime hypoglycemia on a dose of basal insulin that controls fasting blood glucose (FBG). Both of these scenarios lead to obligate snacking, which may fuel insulin-associated weight gain. This problem may be identified by asking about symptoms of hypoglycemia when meals are skipped or snacking to prevent hypoglycemia. Other potential triggers (eg, changes in diet or activity) should be identified. Patients who make significant dietary changes (eg, starting a ketogenic diet) may require substantial reductions in insulin dosing (eg, ≥50 percent reduction).
●Nocturnal hypoglycemia – The dose of basal insulin should be reduced (bedtime dosing if taking twice daily) by 4 units or 10 percent, whichever is greater (algorithm 1). If the patient is taking bedtime NPH, an alternative is to switch to detemir, insulin glargine, or degludec.
Among basal insulin preparations, insulin glargine, detemir, and degludec may have some relatively modest clinical advantages over NPH when pursuing tight glycemic targets (less symptomatic and nocturnal hypoglycemia) with the important disadvantage of high cost. (See 'Choice of basal insulin' above.)
●Daytime hypoglycemia – If the patient is taking prandial insulin, the dose should be decreased at the appropriate meal time(s) by one to three units. The patient should be instructed on how to adjust the prandial dose for meal size and carbohydrate content. In addition, patients should be asked about the timing of their prandial insulin dose and have appropriate timing reinforced if it appears to be contributing to episodes of hypoglycemia (for example, if the patient is taking the insulin following a meal rather than prior to the meal).
If the patient is not taking prandial insulin, the dose of basal insulin should be reduced (by 4 units or 10 percent, whichever is greater) (algorithm 1). If needed (based on self-monitoring of blood glucose), prandial insulin should be added to cover mealtime excursions. If the patient is taking bedtime NPH, an alternative is to switch to insulin glargine or degludec and reduce the total daily basal insulin dose by 10 to 20 percent.
●Severe hypoglycemia – If the patient has a hypoglycemic event requiring the assistance of another person to actively administer carbohydrate (severe hypoglycemia) and there are no apparent changes in diet or activity to account for hypoglycemia, it is prudent to reduce the dose substantially (eg, by 20 to 50 percent) and repeat the titration of the basal insulin.
The management of hypoglycemia in patients with diabetes is reviewed in more detail separately.
Although basal insulin is associated with less hypoglycemia than prandial insulin (see 'Insulin initiation' above), hypoglycemia can occur when the dose of basal insulin is titrated to cover meals. If the patient subsequently eats less than usual, hypoglycemia may occur. Alternatively, some patients develop daytime hypoglycemia on a dose of basal insulin that controls fasting blood glucose (FBG). Both of these scenarios lead to obligate snacking, which may fuel insulin-associated weight gain. This problem may be identified by asking about symptoms of hypoglycemia when meals are skipped or snacking to prevent hypoglycemia. Other potential triggers (eg, changes in diet or activity) should be identified. Patients who make significant dietary changes (eg, starting a ketogenic diet) may require substantial reductions in insulin dosing (eg, ≥50 percent reduction).
●Nocturnal hypoglycemia – The dose of basal insulin should be reduced (bedtime dosing if taking twice daily) by 4 units or 10 percent, whichever is greater (algorithm 1). If the patient is taking bedtime NPH, an alternative is to switch to detemir, insulin glargine, or degludec.
Among basal insulin preparations, insulin glargine, detemir, and degludec may have some relatively modest clinical advantages over NPH when pursuing tight glycemic targets (less symptomatic and nocturnal hypoglycemia) with the important disadvantage of high cost. (See 'Choice of basal insulin' above.)
●Daytime hypoglycemia – If the patient is taking prandial insulin, the dose should be decreased at the appropriate meal time(s) by one to three units. The patient should be instructed on how to adjust the prandial dose for meal size and carbohydrate content. In addition, patients should be asked about the timing of their prandial insulin dose and have appropriate timing reinforced if it appears to be contributing to episodes of hypoglycemia (for example, if the patient is taking the insulin following a meal rather than prior to the meal).
If the patient is not taking prandial insulin, the dose of basal insulin should be reduced (by 4 units or 10 percent, whichever is greater) (algorithm 1). If needed (based on self-monitoring of blood glucose), prandial insulin should be added to cover mealtime excursions. If the patient is taking bedtime NPH, an alternative is to switch to insulin glargine or degludec and reduce the total daily basal insulin dose by 10 to 20 percent.
●Severe hypoglycemia – If the patient has a hypoglycemic event requiring the assistance of another person to actively administer carbohydrate (severe hypoglycemia) and there are no apparent changes in diet or activity to account for hypoglycemia, it is prudent to reduce the dose substantially (eg, by 20 to 50 percent) and repeat the titration of the basal insulin.
The management of hypoglycemia in patients with diabetes is reviewed in more detail separately.
Insulin therapy in type 2 diabetes mellitus TROUBLESHOOTING 1
TROUBLESHOOTING
Insulin resistance — In severely insulin-resistant patients (eg, requiring more than 200 total units of insulin daily), concentrated insulins can be used to control hyperglycemia. Concentrated insulin formulations permit equivalent dosing in smaller volumes and without the need for numerous injections to deliver high doses. Because the high concentration of insulin delays absorption, the pharmacokinetics are often affected. As an example, the pharmacologic profile of U-500 regular insulin is most similar to that of NPH. (See "General principles of insulin therapy in diabetes mellitus", section on 'U-500 regular insulin'.)
Glargine 300 units/mL is very similar to glargine but has a volume one-third of that for the same dose of glargine 100 units/mL. The pharmacokinetics are slightly different, with less of a peak and a longer duration of action. Consequently, glargine 300 units/mL is more similar to degludec than glargine 100 units/mL [50]. (See "General principles of insulin therapy in diabetes mellitus", section on 'U-300 insulin glargine'.)
Insulin-associated weight gain — Patients initiating insulin therapy should be aware of the potential for weight gain, and major emphasis should be placed on diet and lifestyle modification to prevent it. It is important to educate patients about insulin dose reduction for anticipated increases in physical activity and with changes in diet to reduce the risk of hypoglycemia as well as weight gain.
Patients with type 2 diabetes, insulin resistance, and obesity are susceptible to insulin-associated weight gain. This can be due to continued dietary indiscretion, reduction in glycosuria with more physiologic glycemic control, conscious or subconscious snacking to support an insulin dose that is too high, overtreatment of hypoglycemia, overly tight glycemic targets, or a combination of these factors. The resulting weight gain worsens insulin resistance and may prompt insulin dose escalation, leading to a vicious cycle.
The magnitude of the weight gain depends upon the intensity of regimen (dose and frequency of insulin) and the dietary pattern [51]. In the United Kingdom Prospective Diabetes Study (UKPDS), the average weight gain after 10 years of insulin therapy was approximately 7 kg for patients with type 2 diabetes, with the most rapid weight gain occurring when insulin was first initiated [52]. Less intensive therapy with either insulin or a sulfonylurea (which increases endogenous insulin secretion) was associated with a 3.5 to 4.8 kg weight gain at three years versus no change with metformin monotherapy [47]. In a subsequent trial, weight gain was greater with prandial than basal insulin (4.8 versus 3.1 kg) [18]; however, patients receiving prandial insulin also received a greater insulin dose, which could account for the small difference in weight gain. In other trials, pre-mixed rapid-acting preparations were more often associated with weight gain than long-acting insulin or oral agents [44].
It is not clear if the weight gain is important for diabetes complications, as microvascular complications were reduced with insulin monotherapy in the UKPDS despite weight gain [52]. Whether weight gain with insulin might adversely affect risk for cardiovascular disease (CVD) in type 2 diabetes is not clear; however, in type 1 diabetes, intensive insulin therapy in Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) resulted in weight gain but a major reduction in CVD [53]. A subsequent analysis of the DCCT data revealed that the CVD benefit of intensive therapy was attenuated by weight gain [54]. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on 'Diabetes education'.)
Insulin resistance — In severely insulin-resistant patients (eg, requiring more than 200 total units of insulin daily), concentrated insulins can be used to control hyperglycemia. Concentrated insulin formulations permit equivalent dosing in smaller volumes and without the need for numerous injections to deliver high doses. Because the high concentration of insulin delays absorption, the pharmacokinetics are often affected. As an example, the pharmacologic profile of U-500 regular insulin is most similar to that of NPH. (See "General principles of insulin therapy in diabetes mellitus", section on 'U-500 regular insulin'.)
Glargine 300 units/mL is very similar to glargine but has a volume one-third of that for the same dose of glargine 100 units/mL. The pharmacokinetics are slightly different, with less of a peak and a longer duration of action. Consequently, glargine 300 units/mL is more similar to degludec than glargine 100 units/mL [50]. (See "General principles of insulin therapy in diabetes mellitus", section on 'U-300 insulin glargine'.)
Insulin-associated weight gain — Patients initiating insulin therapy should be aware of the potential for weight gain, and major emphasis should be placed on diet and lifestyle modification to prevent it. It is important to educate patients about insulin dose reduction for anticipated increases in physical activity and with changes in diet to reduce the risk of hypoglycemia as well as weight gain.
Patients with type 2 diabetes, insulin resistance, and obesity are susceptible to insulin-associated weight gain. This can be due to continued dietary indiscretion, reduction in glycosuria with more physiologic glycemic control, conscious or subconscious snacking to support an insulin dose that is too high, overtreatment of hypoglycemia, overly tight glycemic targets, or a combination of these factors. The resulting weight gain worsens insulin resistance and may prompt insulin dose escalation, leading to a vicious cycle.
The magnitude of the weight gain depends upon the intensity of regimen (dose and frequency of insulin) and the dietary pattern [51]. In the United Kingdom Prospective Diabetes Study (UKPDS), the average weight gain after 10 years of insulin therapy was approximately 7 kg for patients with type 2 diabetes, with the most rapid weight gain occurring when insulin was first initiated [52]. Less intensive therapy with either insulin or a sulfonylurea (which increases endogenous insulin secretion) was associated with a 3.5 to 4.8 kg weight gain at three years versus no change with metformin monotherapy [47]. In a subsequent trial, weight gain was greater with prandial than basal insulin (4.8 versus 3.1 kg) [18]; however, patients receiving prandial insulin also received a greater insulin dose, which could account for the small difference in weight gain. In other trials, pre-mixed rapid-acting preparations were more often associated with weight gain than long-acting insulin or oral agents [44].
It is not clear if the weight gain is important for diabetes complications, as microvascular complications were reduced with insulin monotherapy in the UKPDS despite weight gain [52]. Whether weight gain with insulin might adversely affect risk for cardiovascular disease (CVD) in type 2 diabetes is not clear; however, in type 1 diabetes, intensive insulin therapy in Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) resulted in weight gain but a major reduction in CVD [53]. A subsequent analysis of the DCCT data revealed that the CVD benefit of intensive therapy was attenuated by weight gain [54]. (See "Initial management of blood glucose in adults with type 2 diabetes mellitus", section on 'Diabetes education'.)
Use of automated insulin algorithms
Use of automated insulin algorithms — In order to achieve glycemic goals, the dose of insulin must be titrated often. Most patients with type 2 diabetes adjust their insulin dose with clinician advice (rather than independently), but the adjustments are made less frequently than necessary, in part due to clinician time constraints. At least one handheld device is under development that contains a glucose meter and uses an insulin algorithm to determine each insulin dose, based on the glucose readings. The software analyzes glucose patterns and adjusts the insulin dose to meet patient needs. In a randomized trial in 181 insulin-requiring patients with type 2 diabetes (mean A1C 8.6 percent), the use of one such device along with clinician support reduced A1C compared with clinician support alone (from baseline to six months, -1 versus -0.3 percentage points) [49]. The frequency of chemical hypoglycemia (glucose <54 mg/dL [3 mmol/L]) was similar in the two groups, whereas weight gain was slightly more in the intervention group (2.3 versus 0.7 percent above baseline). This type of device shows promise for improving glycemic control in patients with type 2 diabetes.
Conversion from twice-daily to once-daily basal insulin
Conversion from twice-daily to once-daily basal insulin — If the patient is taking NPH or detemir twice per day and prefers once-daily basal insulin dosing, a switch to glargine or degludec once daily may be safely done by reducing the total daily basal insulin dose by 10 to 20 percent and re-titrating based on blood glucose levels. If the patient is very hyperglycemic without any hypoglycemia, the equivalent total daily dose may be given as a once-daily long-acting insulin.
Insulin therapy in type 2 diabetes mellitus -Combining prandial and basal insulin
Combining prandial and basal insulin — For patients with type 2 diabetes who require prandial insulin, the goal is to adjust the dose of short-acting or rapid-acting insulin immediately prior to a meal, and therefore, we prefer to keep basal and pre-meal insulin injections separate and adjust them independently. Patients may draw up their pre-meal and NPH insulin in the same syringe prior to injection, whereas glargine, degludec, and detemir cannot be mixed with rapid-acting insulin.
●Choice of prandial insulin – The choice of prandial insulin is based upon availability, patient preference, cost, and payer coverage. The newer rapid-acting insulins have a minor glycemic advantage and the convenience of administration timing closer to the meal over regular insulin in patients with type 1 diabetes, but they do not have a clinically significant advantage in patients with type 2 diabetes [41,42]. This was illustrated in a meta-analysis of 10 randomized trials (involving 2751 patients with type 2 diabetes) that compared rapid-acting insulin analogs with regular insulin as pre-meal bolus doses [42]. No significant differences were seen in serum A1C concentrations or the number of hypoglycemic episodes. However, the ability to inject the rapid-acting insulins immediately before meals (as opposed to the 30 to 45 minutes before the meal recommended for short-acting insulins) may provide improved convenience for patients.
●Pre-meal insulin dosing – The optimal dose of pre-meal insulin depends upon many factors, including current and target blood glucose values, carbohydrate content of the meal, and activity. A typical starting dose is approximately 4 to 6 units (algorithm 1). The dose can be increased by 2 to 3 units every three days until the postprandial blood glucose target is achieved.
A more complex method for adjusting pre-meal insulin is to match insulin delivery to the anticipated glucose excursion with meals. Many patients benefit from specific training in carbohydrate counting, which requires some arithmetical computations that some patients find difficult or burdensome. It is uncertain if there is a glycemic advantage to carbohydrate counting in patients with type 2 diabetes. As an example, in a 24-week, randomized trial in 277 adults with type 2 diabetes, there was no difference in A1C values when mealtime insulin adjustments were based upon a simple algorithm (according to previous weeks' blood glucose monitoring results) versus carbohydrate counting, using an insulin-to-carbohydrate ratio for each meal [43]. Either method is acceptable, and patient preference can guide the choice of method for pre-meal dosing. A simplified adaptation in which patients take a slightly higher dose of prandial insulin for high carbohydrate meals may yield many of the benefits of carbohydrate counting without the complexity and is more straightforward for most patients with type 2 diabetes. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Carbohydrate consistency'.)
●Pre-mixed insulin – Some insulins are commercially available in a pre-mixed formulation. Most pre-mixed (biphasic) preparations contain an intermediate-acting insulin and either a short-acting or a rapid-acting insulin. We suggest not using pre-mixed insulin initially, because of limited flexibility in adjusting doses. However, pre-mixed insulin is a reasonable option for patients with type 2 diabetes who are doing well on a stable, fixed ratio, particularly those who eat a larger breakfast and dinner and a smaller lunch. (See "General principles of insulin therapy in diabetes mellitus", section on 'Pre-mixed insulins'.)
Pre-mixed rapid-acting preparations offer little glycemic advantage compared with adequately titrated basal and bolus insulin. In an open-label trial, 708 patients with type 2 diabetes who were suboptimally controlled with metformin and a sulfonylurea were randomly assigned to pre-mixed biphasic insulin aspart (twice daily), prandial insulin aspart (three times daily), or basal insulin detemir (once or twice daily), there was no difference in median A1C levels among the three groups (7.1, 6.8, and 6.9 percent, respectively), but significantly more patients in the basal and prandial groups achieved an A1C level ≤6.5 percent than in the pre-mixed biphasic group (43, 45, and 32 percent, respectively) [21]. The majority of all three treatment groups used a second type of insulin, per protocol, during the trial to obtain the stipulated glycemic goals. Patients in the basal group had the fewest episodes of hypoglycemia. In other trials, pre-mixed rapid-acting preparations were more often associated with minor hypoglycemia and weight gain than long-acting insulin or oral agents [44].
●Intensive insulin regimens – If intensive insulin therapy is chosen in a patient with type 2 diabetes, the pretreatment considerations, choice of regimen, and management issues are similar to those for patients with type 1 diabetes. Insulin pump therapy is used infrequently in patients with type 2 diabetes, but it may have a role in a select group of patients with poorly controlled type 2 diabetes taking multiple daily injections [45]. In a short-term trial comparing an automated closed-loop insulin delivery system with conventional subcutaneous insulin therapy in hospitalized patients (noncritical care) with type 2 diabetes, a greater proportion of patients receiving pump therapy were in the target range of 100 to 180 mg/dL (5.6 to 10 mmol/L; 65.8 versus 41.5 percent) [46]. However, the mean glucose level was within target range for hospitalized patients in both groups (154 versus 188 mg/dL in the control group [8.5 and 10.4 mmol/L]), and there was no significant difference in duration of hypoglycemia or in the amount of insulin delivered. Whether the modest improvement in glycemic control in noncritical hospitalized patients improves outcomes and is merited, considering the potential increased cost, remains to be demonstrated. Intensive insulin therapy is reviewed in detail elsewhere. (See "Management of blood glucose in adults with type 1 diabetes mellitus".)
Use of an intensive insulin regimen (similar to that used in type 1 diabetes) results in higher serum insulin concentrations and better glycemic control than that achieved with either an oral drug or conventional insulin therapy alone [47]. A potential problem is the weight gain (averaging 8.7 kg in one study) that can occur with intensive regimens that achieve near-normoglycemia [48]. This weight gain may, in some instances, result in partial noncompliance with therapy, particularly in women. (See 'Disadvantages' above and "Nutritional considerations in type 2 diabetes mellitus".)
●Choice of prandial insulin – The choice of prandial insulin is based upon availability, patient preference, cost, and payer coverage. The newer rapid-acting insulins have a minor glycemic advantage and the convenience of administration timing closer to the meal over regular insulin in patients with type 1 diabetes, but they do not have a clinically significant advantage in patients with type 2 diabetes [41,42]. This was illustrated in a meta-analysis of 10 randomized trials (involving 2751 patients with type 2 diabetes) that compared rapid-acting insulin analogs with regular insulin as pre-meal bolus doses [42]. No significant differences were seen in serum A1C concentrations or the number of hypoglycemic episodes. However, the ability to inject the rapid-acting insulins immediately before meals (as opposed to the 30 to 45 minutes before the meal recommended for short-acting insulins) may provide improved convenience for patients.
●Pre-meal insulin dosing – The optimal dose of pre-meal insulin depends upon many factors, including current and target blood glucose values, carbohydrate content of the meal, and activity. A typical starting dose is approximately 4 to 6 units (algorithm 1). The dose can be increased by 2 to 3 units every three days until the postprandial blood glucose target is achieved.
A more complex method for adjusting pre-meal insulin is to match insulin delivery to the anticipated glucose excursion with meals. Many patients benefit from specific training in carbohydrate counting, which requires some arithmetical computations that some patients find difficult or burdensome. It is uncertain if there is a glycemic advantage to carbohydrate counting in patients with type 2 diabetes. As an example, in a 24-week, randomized trial in 277 adults with type 2 diabetes, there was no difference in A1C values when mealtime insulin adjustments were based upon a simple algorithm (according to previous weeks' blood glucose monitoring results) versus carbohydrate counting, using an insulin-to-carbohydrate ratio for each meal [43]. Either method is acceptable, and patient preference can guide the choice of method for pre-meal dosing. A simplified adaptation in which patients take a slightly higher dose of prandial insulin for high carbohydrate meals may yield many of the benefits of carbohydrate counting without the complexity and is more straightforward for most patients with type 2 diabetes. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Carbohydrate consistency'.)
●Pre-mixed insulin – Some insulins are commercially available in a pre-mixed formulation. Most pre-mixed (biphasic) preparations contain an intermediate-acting insulin and either a short-acting or a rapid-acting insulin. We suggest not using pre-mixed insulin initially, because of limited flexibility in adjusting doses. However, pre-mixed insulin is a reasonable option for patients with type 2 diabetes who are doing well on a stable, fixed ratio, particularly those who eat a larger breakfast and dinner and a smaller lunch. (See "General principles of insulin therapy in diabetes mellitus", section on 'Pre-mixed insulins'.)
Pre-mixed rapid-acting preparations offer little glycemic advantage compared with adequately titrated basal and bolus insulin. In an open-label trial, 708 patients with type 2 diabetes who were suboptimally controlled with metformin and a sulfonylurea were randomly assigned to pre-mixed biphasic insulin aspart (twice daily), prandial insulin aspart (three times daily), or basal insulin detemir (once or twice daily), there was no difference in median A1C levels among the three groups (7.1, 6.8, and 6.9 percent, respectively), but significantly more patients in the basal and prandial groups achieved an A1C level ≤6.5 percent than in the pre-mixed biphasic group (43, 45, and 32 percent, respectively) [21]. The majority of all three treatment groups used a second type of insulin, per protocol, during the trial to obtain the stipulated glycemic goals. Patients in the basal group had the fewest episodes of hypoglycemia. In other trials, pre-mixed rapid-acting preparations were more often associated with minor hypoglycemia and weight gain than long-acting insulin or oral agents [44].
●Intensive insulin regimens – If intensive insulin therapy is chosen in a patient with type 2 diabetes, the pretreatment considerations, choice of regimen, and management issues are similar to those for patients with type 1 diabetes. Insulin pump therapy is used infrequently in patients with type 2 diabetes, but it may have a role in a select group of patients with poorly controlled type 2 diabetes taking multiple daily injections [45]. In a short-term trial comparing an automated closed-loop insulin delivery system with conventional subcutaneous insulin therapy in hospitalized patients (noncritical care) with type 2 diabetes, a greater proportion of patients receiving pump therapy were in the target range of 100 to 180 mg/dL (5.6 to 10 mmol/L; 65.8 versus 41.5 percent) [46]. However, the mean glucose level was within target range for hospitalized patients in both groups (154 versus 188 mg/dL in the control group [8.5 and 10.4 mmol/L]), and there was no significant difference in duration of hypoglycemia or in the amount of insulin delivered. Whether the modest improvement in glycemic control in noncritical hospitalized patients improves outcomes and is merited, considering the potential increased cost, remains to be demonstrated. Intensive insulin therapy is reviewed in detail elsewhere. (See "Management of blood glucose in adults with type 1 diabetes mellitus".)
Use of an intensive insulin regimen (similar to that used in type 1 diabetes) results in higher serum insulin concentrations and better glycemic control than that achieved with either an oral drug or conventional insulin therapy alone [47]. A potential problem is the weight gain (averaging 8.7 kg in one study) that can occur with intensive regimens that achieve near-normoglycemia [48]. This weight gain may, in some instances, result in partial noncompliance with therapy, particularly in women. (See 'Disadvantages' above and "Nutritional considerations in type 2 diabetes mellitus".)
DESIGNING AN INSULIN REGIMEN 持續血糖上升如何調整胰島素劑量
餐前胰島素有速效(Insulin Lispro，Insulin Aspart，Insulin Glulisine)和短效(RI)
1.餐前胰島素劑量須考量:
(1)個人胰島素敏感性及餐食的醣類及卡路里量。
(2)起始劑量可為0.1~0.15單位/公斤/每餐，或每單位胰島素控制10~15公克糖類估算。
2.其他注射法:
(1)依固定量，如4單位起跳。
(2)依餐後血糖值，如血糖值(mg/dl)/36(常數)=起始劑量(單位)
(3)依患者體重，0.05單位/公斤/=起始劑量(單位)(瘦小或胰島素敏感者)。
(4)依基礎胰島素(BI)劑量，如BI劑量(單位)X10%=起始劑量(單位)
3.調校方法:
(1)餐後血糖值超標，依固定量增加。如>140mg/dl，增加一單位。
(2)依餐後血糖值，如
如果平均空腹血糖超過 130, 每隔三天以上調整一次劑量, 每次增加 2-4 u. 調整胰島素劑量可能要數周至數個月的時間, 如果空腹血糖超過 250, 或已知病患胰島素抗性高, 可更積極的調整劑量, 但要做低血糖衛教
If the mean FBG is above target (typically 130 mg/dL [7.2 mmol/L]), an increase of 2 to 4 units in the basal insulin dose should be made periodically (approximately every three days) (algorithm 1) [36]. In this way, the basal insulin dose can be titrated over a period of several weeks or months. If FBG levels are very elevated (>250 mg/dL [13.9 mmol/L]) or if a patient is known to be very insulin resistant, titration can be more aggressive. Patients should reduce their insulin dose if hypoglycemia develops.
在病患接近血糖控制目標的時候, 如果病患晚上自然醒過來, 可以順便測一下睡眠之間的血糖, 以排除低血糖
As patients approach the glycemic target, it may be helpful to check a mid-sleep blood glucose to rule out hypoglycemia (this can be done when the patient spontaneously wakes overnight).
如果空腹血糖有達標(80-130或依照病患狀況設定不同標準), 但A1C 仍高, 建議病患測量空腹血糖(睡醒之後吃早餐之前), 午餐前血糖, 晚餐前血糖, 睡前血糖, 隨餐血糖可以挑選一天之中吃的最豐盛的一餐施打
也可以使用連續偵測血糖的血糖機, 測量兩周血糖,
Persistent elevation in A1C with FBG in target range — For patients with persistently elevated glycated hemoglobin (A1C) levels who have fasting blood glucose (FBG) levels in the target range (80 to 130 mg/dL [4.4 to 7.2 mmol/L], or higher, depending on the individualized glycemic target), we advise the patient to check fingerstick capillary glucose levels fasting, pre-lunch, pre-dinner, and before bed while the insulin regimen is further adjusted. Prandial insulin may be started as a single injection before the largest meal of the day, but many strategies are possible (algorithm 1). Short-term monitoring with continuous glucose monitoring for two weeks may also be helpful in insulin dose adjustment. (See "Self-monitoring of glucose in management of nonpregnant adults with diabetes mellitus".)
如果經過胰島素調整, 仍無法將 A1C 降到目標值, 需回顧一下患者的飲食與運動習慣, 建議患者常規測早上空腹血糖, 午餐前及晚餐前及睡前血糖. 一般來說, 胰島素治療失敗通常是由於沒有節制飲食或吃到不該吃的食物造成. 這類情況通常胰島素用量會超過每天 65-100u. 有時候在第二型糖尿病合併肥胖患者會更高.
Among patients whose A1C values remain above the desired target despite insulin adjustments, diet and exercise patterns should be reviewed. We advise the patient to continue to check fingerstick capillary glucose levels fasting, pre-lunch, pre-dinner, and before bed while the regimen is further adjusted. In general, dietary indiscretion and/or mismatch of food and insulin dose underlie the apparent failure of many patients treated with insulin regimens. Daily insulin doses typically exceed 65 to 100 units per day and may sometimes be much higher in patients with type 2 diabetes and obesity.
晚餐前血糖上升, 治療選擇包括在早餐時增加第二劑 detemir or NPH, 如果患者已經在施打 glargine or degludec, 可以增加隨餐胰島素. 另外, 調整午餐的飲食習慣也有效果.
Pre-dinner glucose elevated — If pre-dinner glucose values are elevated, options include adding second dose of detemir or NPH at breakfast or, if the patient is on glargine or degludec, adding prandial insulin at lunch. Dietary modification at lunch may also be effective.
如果治療目標是使用簡單便宜的方式控制持續性高血糖, 一天打兩次 NPH 或 detemir insulin 對於多數人而言是有效的選擇. 當使用 detemir, 一天兩次能更穩定的控制 24小時血糖.
If the goal is control of persistent hyperglycemia with a regimen that is simple and inexpensive, then twice-daily NPH or detemir insulin will be effective in many patients [37,39]. When the insulin preparation is detemir, glycemic control over a 24-hour period may also be more stable in patients taking two doses daily.
午餐前或睡前血糖上升, 可在早餐前或晚餐前加上隨餐胰島素, 包括短效或速效的胰島素, 這種狀況, 建議停止 metformin 以外的其他藥物 (如無其他禁忌症, 或耐受不良, 可持續服用 metformin)
Pre-lunch or bedtime glucose elevated — If blood glucose values are elevated before lunch and/or bed, we typically add prandial insulin. Either short-acting (regular) or rapid-acting insulin can be given before breakfast and/or dinner. In this setting, oral agents other than metformin are discontinued (in the absence of contraindications or intolerance, metformin can be continued).
DESIGNING AN INSULIN REGIMEN 胰島素劑量 Initial dose
控制血糖的目標與步驟
第一步是控制早餐前空腹血糖, 如果早上AC glucone正常, 而A1C 仍超標, 進行第二步
第二步是控制每餐前的血糖, 如果餐前血糖已經達標, 但 A1C 仍超標, 進行第三步
第三步是控制每餐後的血糖, 如果餐後血糖高, 則追加餐前速效胰島素
Insulin Initial dose
Insulin detemir= IDet
Insulin degludec= IDeg
glargine = Gla
第二型糖尿病的胰島素初始劑量相似, (不管是否有服用口服藥, 或以 insulin 替代口服藥, 或使用胰島素做為起始治療方式), 有很多流程圖被發表, 在此提供一種簡易保守的流程.
睡前施打 NPH 或 IDet, 如果病患早上 7-8 AM 測空腹血糖, 往前推 9-10 小時, 施打時間為晚上 10 點.
睡前或早上施打 GLA or IDeg
Gla與IDeg 可以在一天的任何時間施打, 施打 Gla or IDeg 的時間可根據病患喜好做決定, 以提高順從性.
NPH, IDet, Gla 起始劑量都是 0.2u/kg/day., 最低劑量從 10u/day 開始,
IDeg 的起始劑量是 10u/day, 皮下注射
如果空腹血糖 FBG 超過 250, 或已知病患有很高的胰島素阻抗, 初始劑量可以更高
每天測量 FBG, 每三個月測 A1C, 調整藥物劑量
已經使用基礎胰島素, A1C 仍超標, 可測量每餐之前的血糖值
午餐前血糖高 --> 早上施打速效胰島素
晚餐前血糖高--> 早上餐前打NPH 或 午餐前打速效胰島素
睡前血糖高 --> 晚餐前打速效胰島素
For patients with type 2 diabetes, the initial dose of insulin (whether in addition to oral agents, in place of oral agents, or as initial treatment) is similar . Many algorithms have been published; one simple and conservative algorithm is presented here (algorithm 1). We start with bedtime NPH or detemir, taken at 10:00 PM if the person is testing his or her FBG at 7:00 or 8:00 AM, or bedtime or morning glargine or degludec. Since glargine and degludec can be administered any time of day, the timing of daily insulin glargine or degludec is based on patient preference to facilitate adherence. The initial dose for NPH, detemir, or glargine is 0.2 units per kg (minimum 10 units) daily. The initial dose for insulin degludec is 10 units subcutaneously once daily. If FBG levels are very elevated (>250 mg/dL [13.9 mmol/L]), or if a patient is known to be very insulin resistant, initial doses can be higher. Subsequent modifications can be made according to daily measurement of FBG and every three month A1C values.
組合療法- 同時使用口服抗糖尿病藥物與注射胰島素, 藉由不同作用機轉, 達到降血糖的目標, 將胰島素所需總劑量減至最低, 避免體重上升.
加入胰島素治療後, Metformin 通常繼續服用, 其他可以繼續使用的藥物包括, SU, TZD, GLP-RA, DPP-4 inhibitors, SGLT2 inhibitors, 但組合治療的好處, 要與複雜處方及昂貴花費做權衡,
SU 通常逐漸減量停用. 尤其是開始使用隨餐胰島素之後.
●Combination therapy – The rationale for combination oral hypoglycemic drug and insulin therapy is that using glucose-lowering medications with different mechanisms of action may achieve goal glycemia while minimizing total insulin requirements and weight gain [38]. Metformin is often continued with the addition of insulin. Other agents including sulfonylureas, thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors can also be continued when insulin is added, although the putative advantages of doing so must be balanced against the downside of regimen complexity (polypharmacy) and increased cost. Sulfonylureas are usually tapered and stopped, especially when prandial insulin is started.
胰島素單一療法- 使用胰島素單一療法可能比口服藥搭配胰島素便宜 (metformin 不貴), 但可能導致輕微體重上升(取決於所選藥物), 低血糖事件更多, 少數可能很嚴重
病患開始使用胰島素之後, 或者基礎胰島素劑量調整適當之後, 口服藥物可停用,
較早停藥可能造成血糖短暫上升, 直到胰島素調整至適當劑量之後.
●Insulin monotherapy – Switching to insulin monotherapy may be cheaper than combined oral agent-insulin therapy depending on the combination used (metformin is very inexpensive) but may result in slightly more weight gain, depending on the combination, and more episodes of hypoglycemia, few of which are severe [38]. The oral agent may be discontinued when insulin is initially added or after the patient is on adequate basal insulin. The former approach may be associated with elevations in glucose levels until the dose of injected insulin is sufficient to achieve metabolic control.
胰島素劑量調整, 根據 FBG 和 A1C 數值調整, 對於多數第二型糖尿病患, 單獨使用基礎胰島素就可以維持良好血糖控制, 因為身體自己產生的胰島素可以控制飯後血糖波動,
但對於飯後高血糖導致的 A1C 持續上升, 可能需加上餐前胰島素, 與第一型糖尿病治療相似
使用餐前胰島素需自我監測血糖, 不僅是FBG, 例如, 施打餐前胰島素的時候, 測每餐前的血糖, 來調整餐前劑量(餐前劑量應該是指長效胰島素/基礎胰島素)
Titrating dose — The basal insulin regimen is adjusted based on FBG and A1C values. For many patients with type 2 diabetes, basal insulin alone is often adequate for good glycemic control since endogenous insulin secretion will control the postprandial excursions. However, patients with type 2 diabetes and persistently elevated A1C due to postprandial hyperglycemia may require additional pre-meal insulin, similar to treatment for type 1 diabetes. Pre-meal insulin regimens will require self-monitoring of glucose levels other than just fasting levels (ie, before the meals when rapid-acting insulin is used to help determine and subsequently adjust preprandial dosing).
第一步是控制早餐前空腹血糖, 如果早上AC glucone正常, 而A1C 仍超標, 進行第二步
第二步是控制每餐前的血糖, 如果餐前血糖已經達標, 但 A1C 仍超標, 進行第三步
第三步是控制每餐後的血糖, 如果餐後血糖高, 則追加餐前速效胰島素
Insulin Initial dose
Insulin detemir= IDet
Insulin degludec= IDeg
glargine = Gla
第二型糖尿病的胰島素初始劑量相似, (不管是否有服用口服藥, 或以 insulin 替代口服藥, 或使用胰島素做為起始治療方式), 有很多流程圖被發表, 在此提供一種簡易保守的流程.
睡前施打 NPH 或 IDet, 如果病患早上 7-8 AM 測空腹血糖, 往前推 9-10 小時, 施打時間為晚上 10 點.
睡前或早上施打 GLA or IDeg
Gla與IDeg 可以在一天的任何時間施打, 施打 Gla or IDeg 的時間可根據病患喜好做決定, 以提高順從性.
NPH, IDet, Gla 起始劑量都是 0.2u/kg/day., 最低劑量從 10u/day 開始,
IDeg 的起始劑量是 10u/day, 皮下注射
如果空腹血糖 FBG 超過 250, 或已知病患有很高的胰島素阻抗, 初始劑量可以更高
每天測量 FBG, 每三個月測 A1C, 調整藥物劑量
已經使用基礎胰島素, A1C 仍超標, 可測量每餐之前的血糖值
午餐前血糖高 --> 早上施打速效胰島素
晚餐前血糖高--> 早上餐前打NPH 或 午餐前打速效胰島素
睡前血糖高 --> 晚餐前打速效胰島素
For patients with type 2 diabetes, the initial dose of insulin (whether in addition to oral agents, in place of oral agents, or as initial treatment) is similar . Many algorithms have been published; one simple and conservative algorithm is presented here (algorithm 1). We start with bedtime NPH or detemir, taken at 10:00 PM if the person is testing his or her FBG at 7:00 or 8:00 AM, or bedtime or morning glargine or degludec. Since glargine and degludec can be administered any time of day, the timing of daily insulin glargine or degludec is based on patient preference to facilitate adherence. The initial dose for NPH, detemir, or glargine is 0.2 units per kg (minimum 10 units) daily. The initial dose for insulin degludec is 10 units subcutaneously once daily. If FBG levels are very elevated (>250 mg/dL [13.9 mmol/L]), or if a patient is known to be very insulin resistant, initial doses can be higher. Subsequent modifications can be made according to daily measurement of FBG and every three month A1C values.
組合療法- 同時使用口服抗糖尿病藥物與注射胰島素, 藉由不同作用機轉, 達到降血糖的目標, 將胰島素所需總劑量減至最低, 避免體重上升.
加入胰島素治療後, Metformin 通常繼續服用, 其他可以繼續使用的藥物包括, SU, TZD, GLP-RA, DPP-4 inhibitors, SGLT2 inhibitors, 但組合治療的好處, 要與複雜處方及昂貴花費做權衡,
SU 通常逐漸減量停用. 尤其是開始使用隨餐胰島素之後.
●Combination therapy – The rationale for combination oral hypoglycemic drug and insulin therapy is that using glucose-lowering medications with different mechanisms of action may achieve goal glycemia while minimizing total insulin requirements and weight gain [38]. Metformin is often continued with the addition of insulin. Other agents including sulfonylureas, thiazolidinediones, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose co-transporter 2 (SGLT2) inhibitors can also be continued when insulin is added, although the putative advantages of doing so must be balanced against the downside of regimen complexity (polypharmacy) and increased cost. Sulfonylureas are usually tapered and stopped, especially when prandial insulin is started.
胰島素單一療法- 使用胰島素單一療法可能比口服藥搭配胰島素便宜 (metformin 不貴), 但可能導致輕微體重上升(取決於所選藥物), 低血糖事件更多, 少數可能很嚴重
病患開始使用胰島素之後, 或者基礎胰島素劑量調整適當之後, 口服藥物可停用,
較早停藥可能造成血糖短暫上升, 直到胰島素調整至適當劑量之後.
●Insulin monotherapy – Switching to insulin monotherapy may be cheaper than combined oral agent-insulin therapy depending on the combination used (metformin is very inexpensive) but may result in slightly more weight gain, depending on the combination, and more episodes of hypoglycemia, few of which are severe [38]. The oral agent may be discontinued when insulin is initially added or after the patient is on adequate basal insulin. The former approach may be associated with elevations in glucose levels until the dose of injected insulin is sufficient to achieve metabolic control.
胰島素劑量調整, 根據 FBG 和 A1C 數值調整, 對於多數第二型糖尿病患, 單獨使用基礎胰島素就可以維持良好血糖控制, 因為身體自己產生的胰島素可以控制飯後血糖波動,
但對於飯後高血糖導致的 A1C 持續上升, 可能需加上餐前胰島素, 與第一型糖尿病治療相似
使用餐前胰島素需自我監測血糖, 不僅是FBG, 例如, 施打餐前胰島素的時候, 測每餐前的血糖, 來調整餐前劑量(餐前劑量應該是指長效胰島素/基礎胰島素)
Titrating dose — The basal insulin regimen is adjusted based on FBG and A1C values. For many patients with type 2 diabetes, basal insulin alone is often adequate for good glycemic control since endogenous insulin secretion will control the postprandial excursions. However, patients with type 2 diabetes and persistently elevated A1C due to postprandial hyperglycemia may require additional pre-meal insulin, similar to treatment for type 1 diabetes. Pre-meal insulin regimens will require self-monitoring of glucose levels other than just fasting levels (ie, before the meals when rapid-acting insulin is used to help determine and subsequently adjust preprandial dosing).
DESIGNING AN INSULIN REGIMEN 基礎胰島素的選擇 Choice of basal insulin
口服藥治療無法達標時，GLP1受體促效劑優於胰島素使用
Choice of basal insulin —
不管是 insulin NPH 或 detemir, 睡前施打, 或 insulin glargine or degludec 早上或睡前施打, 都是合理的處方, 實際情況, 保險公司是否支付費用, 經常是選擇基礎胰島素的重要考量, 有些國家有 NPL, 可做為單獨處方, 在美國, NPL 只有組合劑型, 與速效胰島素 lispro 組合使用.
A single daily dose of either insulin NPH or detemir given at bedtime or insulin glargine or degludec given in the morning or at bedtime is a reasonable initial regimen (table 1). In practice, payer coverage is often an important consideration in the selection of basal insulin. In some countries, NPL is available as a separate insulin analog for basal coverage [22,23]. In the United States, NPL is only available in combination with rapid-acting lispro (insulin lispro protamine-insulin lispro).
NPL 精蛋白鋅賴脯胰島素，中效胰島素類似物
基礎胰島素對於控糖效果並無差異, 其中 insulin glargine, detemir, and degludec 這三種與 NPH 比較, 發生夜間低血糖機率較低 (並非減少所有低血糖事件), 對大缺點是貴. 而對於低血糖相關住院或送急診機率並無差異.
The basal insulin preparations do not differ significantly in glycemic efficacy [24,25]. Among basal insulin preparations, insulin glargine, detemir, and degludec may have less nocturnal hypoglycemia (but not always total hypoglycemia) compared with NPH, with the important disadvantage of high cost. There does not appear to be any difference in hypoglycemia-related hospital admissions or emergency department visits. As examples:
這篇綜合分析的研究, insulin glargine QD 或 detemir QD BID , 與NPH QD or BID 做比較, 所有基礎胰島素對於 A1C 改善結果相近, 但在某些綜合分析研究, 所有有症狀低血糖及夜間低血糖機率, 使用 insulin glargine or detemir, 比 NPH 低.
●In meta-analyses of trials comparing once-daily insulin glargine or detemir with once-daily or twice-daily NPH insulin, there were similar improvements in A1C with all types of basal insulin [25-28]. However, in some of the meta-analyses, the rates of overall symptomatic and nocturnal hypoglycemia (while relatively infrequent with either basal insulin) were lower in patients treated with either insulin glargine or detemir compared with NPH [25-27].
一項利用健康系統大數據的回溯性觀察性研究發現, 胰島素類似物與NPH做比較, 低血糖送急診或低血糖住院率並無差異(11.9 VS 8.8 每千人每年次數), 但 NPH 這組的血糖控制稍微好些 (A1C 8.2 vs 7.9%)
●In a retrospective observational study using data from a large health care delivery system (>25,000 patients initiating basal insulin), there was no benefit of insulin analogs compared with NPH in reducing emergency department or hospital admissions for hypoglycemia (11.9 versus 8.8 events per 1000 person-years, respectively) despite slightly better glycemic control in the NPH group (achieved A1C 8.2 versus 7.9 percent with NPH, suggesting they were not treated with less aggressive doses) [29].
Insulin degludec (IDeg)控制血糖效果與 insulin glargine 相似, 在某些研究中, IDeg 發生低血糖的機率較低, 在嚴格控制血糖的患者更是如此, 一篇斷代研究, 雙盲試驗, 收錄721位成年第二型糖尿病患者, 患者至少有一種低血糖的危險因子, 平均血色素 A1C 7.6%, 隨機分配至 IDeg QD 與 Gla QD. 經過 32 周治療, 再換另一種替代胰島素繼續治療 32周,
全部有症狀低血糖事件: IDeg 185.6 , Gla 265.4 (次/100 人-年)
夜間有症狀低血糖事件 IDeg 55.2 , Gla 93.6 (次/100 人-年)
IDeg 全部有症狀低血糖事件機率較低 (機率是 Gla 組的 0.70 倍).
IDeg 夜間有症狀低血糖事件機率較低 (機率是 Gla 組的 0.58 倍)
兩組發生嚴重低血糖的機率都不高且相近 (IDeg組減少 0.74 次/100人年),
兩組控制血糖效果相似 (A1C 7% to 7.1%)
Insulin degludec appears to have similar glycemic efficacy as that of insulin glargine and, in some trials, a lower rate of hypoglycemia, especially if aiming for more stringent glycemic targets [17,30-33]. As an example, in a 65-week, double-blind, crossover trial, 721 adults with type 2 diabetes (mean A1C 7.6 percent) and at least one risk factor for hypoglycemia were randomly assigned to receive once-daily insulin degludec or insulin glargine for 32 weeks and then crossed over to the alternate insulin treatment for the next 32 weeks [34]. The rate of overall (185.6 versus 265.4 episodes per 100 patient-years of exposure) and nocturnal (55.2 versus 93.6 episodes) symptomatic hypoglycemia was lower with degludec (rate ratios 0.70, 95% CI 0.61-0.80 and 0.58, 95% CI 0.46-0.74, respectively). There was no difference in relatively rare severe hypoglycemia (nonsignificant reduction of 0.62 episodes per 100 patient-years with degludec). Overall glycemic control was similar (A1C 7 to 7.1 percent).
雖然 IDeg 明顯減少所有低血糖與夜間低血糖, 其效益需與費用做權衡, (平均每五年降低一次低血糖事件), IDeg 的長期安全性仍未明.
Although degludec significantly reduced overall and nocturnal hypoglycemia, the modest benefit (on average, one episode less every five years) must be balanced against its relatively higher cost. In addition, the long-term safety profile of insulin degludec is unknown
Choice of basal insulin —
不管是 insulin NPH 或 detemir, 睡前施打, 或 insulin glargine or degludec 早上或睡前施打, 都是合理的處方, 實際情況, 保險公司是否支付費用, 經常是選擇基礎胰島素的重要考量, 有些國家有 NPL, 可做為單獨處方, 在美國, NPL 只有組合劑型, 與速效胰島素 lispro 組合使用.
A single daily dose of either insulin NPH or detemir given at bedtime or insulin glargine or degludec given in the morning or at bedtime is a reasonable initial regimen (table 1). In practice, payer coverage is often an important consideration in the selection of basal insulin. In some countries, NPL is available as a separate insulin analog for basal coverage [22,23]. In the United States, NPL is only available in combination with rapid-acting lispro (insulin lispro protamine-insulin lispro).
NPL 精蛋白鋅賴脯胰島素，中效胰島素類似物
基礎胰島素對於控糖效果並無差異, 其中 insulin glargine, detemir, and degludec 這三種與 NPH 比較, 發生夜間低血糖機率較低 (並非減少所有低血糖事件), 對大缺點是貴. 而對於低血糖相關住院或送急診機率並無差異.
The basal insulin preparations do not differ significantly in glycemic efficacy [24,25]. Among basal insulin preparations, insulin glargine, detemir, and degludec may have less nocturnal hypoglycemia (but not always total hypoglycemia) compared with NPH, with the important disadvantage of high cost. There does not appear to be any difference in hypoglycemia-related hospital admissions or emergency department visits. As examples:
這篇綜合分析的研究, insulin glargine QD 或 detemir QD BID , 與NPH QD or BID 做比較, 所有基礎胰島素對於 A1C 改善結果相近, 但在某些綜合分析研究, 所有有症狀低血糖及夜間低血糖機率, 使用 insulin glargine or detemir, 比 NPH 低.
●In meta-analyses of trials comparing once-daily insulin glargine or detemir with once-daily or twice-daily NPH insulin, there were similar improvements in A1C with all types of basal insulin [25-28]. However, in some of the meta-analyses, the rates of overall symptomatic and nocturnal hypoglycemia (while relatively infrequent with either basal insulin) were lower in patients treated with either insulin glargine or detemir compared with NPH [25-27].
一項利用健康系統大數據的回溯性觀察性研究發現, 胰島素類似物與NPH做比較, 低血糖送急診或低血糖住院率並無差異(11.9 VS 8.8 每千人每年次數), 但 NPH 這組的血糖控制稍微好些 (A1C 8.2 vs 7.9%)
●In a retrospective observational study using data from a large health care delivery system (>25,000 patients initiating basal insulin), there was no benefit of insulin analogs compared with NPH in reducing emergency department or hospital admissions for hypoglycemia (11.9 versus 8.8 events per 1000 person-years, respectively) despite slightly better glycemic control in the NPH group (achieved A1C 8.2 versus 7.9 percent with NPH, suggesting they were not treated with less aggressive doses) [29].
Insulin degludec (IDeg)控制血糖效果與 insulin glargine 相似, 在某些研究中, IDeg 發生低血糖的機率較低, 在嚴格控制血糖的患者更是如此, 一篇斷代研究, 雙盲試驗, 收錄721位成年第二型糖尿病患者, 患者至少有一種低血糖的危險因子, 平均血色素 A1C 7.6%, 隨機分配至 IDeg QD 與 Gla QD. 經過 32 周治療, 再換另一種替代胰島素繼續治療 32周,
全部有症狀低血糖事件: IDeg 185.6 , Gla 265.4 (次/100 人-年)
夜間有症狀低血糖事件 IDeg 55.2 , Gla 93.6 (次/100 人-年)
IDeg 全部有症狀低血糖事件機率較低 (機率是 Gla 組的 0.70 倍).
IDeg 夜間有症狀低血糖事件機率較低 (機率是 Gla 組的 0.58 倍)
兩組發生嚴重低血糖的機率都不高且相近 (IDeg組減少 0.74 次/100人年),
兩組控制血糖效果相似 (A1C 7% to 7.1%)
Insulin degludec appears to have similar glycemic efficacy as that of insulin glargine and, in some trials, a lower rate of hypoglycemia, especially if aiming for more stringent glycemic targets [17,30-33]. As an example, in a 65-week, double-blind, crossover trial, 721 adults with type 2 diabetes (mean A1C 7.6 percent) and at least one risk factor for hypoglycemia were randomly assigned to receive once-daily insulin degludec or insulin glargine for 32 weeks and then crossed over to the alternate insulin treatment for the next 32 weeks [34]. The rate of overall (185.6 versus 265.4 episodes per 100 patient-years of exposure) and nocturnal (55.2 versus 93.6 episodes) symptomatic hypoglycemia was lower with degludec (rate ratios 0.70, 95% CI 0.61-0.80 and 0.58, 95% CI 0.46-0.74, respectively). There was no difference in relatively rare severe hypoglycemia (nonsignificant reduction of 0.62 episodes per 100 patient-years with degludec). Overall glycemic control was similar (A1C 7 to 7.1 percent).
雖然 IDeg 明顯減少所有低血糖與夜間低血糖, 其效益需與費用做權衡, (平均每五年降低一次低血糖事件), IDeg 的長期安全性仍未明.
Although degludec significantly reduced overall and nocturnal hypoglycemia, the modest benefit (on average, one episode less every five years) must be balanced against its relatively higher cost. In addition, the long-term safety profile of insulin degludec is unknown
DESIGNING AN INSULIN REGIMEN 基礎胰島素與隨餐胰島素
from uptodate
DESIGNING AN INSULIN REGIMEN
臨床醫師應該要對幾種糖尿病的治療很熟悉, 始終如一的使用.
We advise clinicians to familiarize themselves with a limited number of regimens 養生之道 (to facilitate addressing 對病患說 patient preferences個人偏好, lifestyle [meal and activity patterns], etc) and use them consistently.
經過適當調整劑量後, 不同胰島素對於降血糖的效果差異不大.
在現實的治療, 基礎胰島素的劑量經常使用不足,
多數的研究僅能提供各種胰島素的降血糖效果, 對於不同種類的胰島素, 微細血管及大血管併發症或死亡率的資訊未能提供. 對於降低A1C的差異, 有時候會被不良反應(低血糖)抵銷.
The glycemic differences achieved among different insulin regimens, assuming that they are adequately titrated, are modest. However, basal insulin is frequently suboptimally titrated in actual clinical practice [19]. The majority of the studies provide information on lowering of glycemia but do not provide information regarding the effects of various insulin regimens on microvascular or macrovascular complications or mortality. When differences in A1C levels have been found, they are sometimes offset by adverse events such as hypoglycemia.
對於即將使用胰島素的病患, 建議選擇基礎胰島素, 而非隨餐胰島素, 基礎胰島素可以改善夜間血糖及空腹血糖, 餐前胰島素可以降低餐後血糖波動,
基礎胰島素與隨餐胰島素, 何者更能改善小血管併發症仍未知.
不同種類的胰島素對於心血管併發症的影響並無差異.
Insulin initiation — For patients who are initiating insulin (in addition to oral agents, in place of oral agents, or as initial treatment), we suggest initiating basal, rather than prandial, insulin. Basal insulin will improve nocturnal and fasting blood glucose (空腹血糖 FBG), whereas prandial (pre-meal) bolus insulin will decrease postprandial glucose excursions. Whether a basal or a prandial strategy is more effective in improving microvascular complications remains uncertain. The type of insulin regimen (basal or prandial) does not appear to affect cardiovascular outcomes.
使用基礎胰島素做為起始治療, 優點是方便, 簡單, 尤其是第一次使用胰島素的病患, 雖然基礎胰島素與隨餐胰島素, 針對治療目標積極調整劑量之後, 對於降低 A1C 的結果相似, 基礎胰島素的病患滿意度較高, 低血糖機率較低
Initiation of insulin therapy with a basal insulin has the advantage of convenience and simplicity in patients who are using insulin for the first time. Although basal and prandial insulin are similarly effective in improving A1C when insulin doses are aggressively titrated to achieve glycemic goals, basal insulin is associated with greater patient satisfaction and less frequent hypoglycemia [20,21]. As examples:
隨機研究, 收錄經過 metformin 及 SU 治療後, 血糖仍控制不良的患者, 共收錄 415位, , 一天打一次 insulin glargine 與隨餐胰島素 lispro 比較, 最後降低 A1C 的結果相近(1.7 VS 1.9), 兩組之中, A1C 降低至6.5~7.0 的人數比例, 分別是 27% VS 30%, 基礎胰島素的病患滿意度較高, 低血糖事件較少
●In a randomized trial of once-daily insulin glargine versus prandial insulin lispro in 415 patients who were inadequately controlled with metformin and a sulfonylurea, there were similar improvements in A1C (mean decrease of 1.7 and 1.9 percent, respectively) and target A1C concentrations between 6.5 and 7.0 percent were achieved by 27 and 30 percent of subjects, respectively [20]. Basal insulin was associated with greater patient satisfaction and less hypoglycemia.
這篇研究標題是第二型糖尿病患, 高血糖對於急性心肌梗塞後的心血管結果之影響, 簡稱 HEART2D 研究, 實驗設計是為了評估隨餐血糖 lispro 與基礎胰島素 NPH BID 或 insulin glargine QD, 對於病患心血管結果的影響, 總共收錄 1115 位心肌梗塞之後的病患, 實驗開始時, 有 50% 病患使用 metformin 和 SU, 單獨使用或兩個並用, 其他病患則使用胰島素做為單一治療. 追蹤2.7年後, 因為兩者沒有太大差異使得研究提早結束, 兩組對於 A1C 分別降到 7.7% VS 7.8%, 對於 cardiovascular outcomes 心血管結果的影響差異不大
cardiovascular event 心血管事件包括: 心血管死亡, 非致死性心肌梗塞, 非致死性中風, 冠狀動脈血管重建, 因急性冠心症住院)
(cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for an acute coronary syndrome).)
●The Hyperglycemia and its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus (HEART2D) trial was designed to evaluate the effects of prandial (lispro) or basal (NPH twice daily or insulin glargine once daily) insulin on cardiovascular outcomes in 1115 patients after myocardial infarction (MI) [18]. At baseline, 50 percent of the patients were taking metformin, sulfonylureas, or both, whereas the remaining patients were treated with insulin monotherapy. At a mean follow-up of 2.7 years, the trial was stopped early due to lack of efficacy. There was no difference between the prandial and basal groups in A1C (7.7 versus 7.8 percent). The cardiovascular outcomes are reviewed above.
DESIGNING AN INSULIN REGIMEN
臨床醫師應該要對幾種糖尿病的治療很熟悉, 始終如一的使用.
We advise clinicians to familiarize themselves with a limited number of regimens 養生之道 (to facilitate addressing 對病患說 patient preferences個人偏好, lifestyle [meal and activity patterns], etc) and use them consistently.
經過適當調整劑量後, 不同胰島素對於降血糖的效果差異不大.
在現實的治療, 基礎胰島素的劑量經常使用不足,
多數的研究僅能提供各種胰島素的降血糖效果, 對於不同種類的胰島素, 微細血管及大血管併發症或死亡率的資訊未能提供. 對於降低A1C的差異, 有時候會被不良反應(低血糖)抵銷.
The glycemic differences achieved among different insulin regimens, assuming that they are adequately titrated, are modest. However, basal insulin is frequently suboptimally titrated in actual clinical practice [19]. The majority of the studies provide information on lowering of glycemia but do not provide information regarding the effects of various insulin regimens on microvascular or macrovascular complications or mortality. When differences in A1C levels have been found, they are sometimes offset by adverse events such as hypoglycemia.
對於即將使用胰島素的病患, 建議選擇基礎胰島素, 而非隨餐胰島素, 基礎胰島素可以改善夜間血糖及空腹血糖, 餐前胰島素可以降低餐後血糖波動,
基礎胰島素與隨餐胰島素, 何者更能改善小血管併發症仍未知.
不同種類的胰島素對於心血管併發症的影響並無差異.
Insulin initiation — For patients who are initiating insulin (in addition to oral agents, in place of oral agents, or as initial treatment), we suggest initiating basal, rather than prandial, insulin. Basal insulin will improve nocturnal and fasting blood glucose (空腹血糖 FBG), whereas prandial (pre-meal) bolus insulin will decrease postprandial glucose excursions. Whether a basal or a prandial strategy is more effective in improving microvascular complications remains uncertain. The type of insulin regimen (basal or prandial) does not appear to affect cardiovascular outcomes.
使用基礎胰島素做為起始治療, 優點是方便, 簡單, 尤其是第一次使用胰島素的病患, 雖然基礎胰島素與隨餐胰島素, 針對治療目標積極調整劑量之後, 對於降低 A1C 的結果相似, 基礎胰島素的病患滿意度較高, 低血糖機率較低
Initiation of insulin therapy with a basal insulin has the advantage of convenience and simplicity in patients who are using insulin for the first time. Although basal and prandial insulin are similarly effective in improving A1C when insulin doses are aggressively titrated to achieve glycemic goals, basal insulin is associated with greater patient satisfaction and less frequent hypoglycemia [20,21]. As examples:
隨機研究, 收錄經過 metformin 及 SU 治療後, 血糖仍控制不良的患者, 共收錄 415位, , 一天打一次 insulin glargine 與隨餐胰島素 lispro 比較, 最後降低 A1C 的結果相近(1.7 VS 1.9), 兩組之中, A1C 降低至6.5~7.0 的人數比例, 分別是 27% VS 30%, 基礎胰島素的病患滿意度較高, 低血糖事件較少
●In a randomized trial of once-daily insulin glargine versus prandial insulin lispro in 415 patients who were inadequately controlled with metformin and a sulfonylurea, there were similar improvements in A1C (mean decrease of 1.7 and 1.9 percent, respectively) and target A1C concentrations between 6.5 and 7.0 percent were achieved by 27 and 30 percent of subjects, respectively [20]. Basal insulin was associated with greater patient satisfaction and less hypoglycemia.
這篇研究標題是第二型糖尿病患, 高血糖對於急性心肌梗塞後的心血管結果之影響, 簡稱 HEART2D 研究, 實驗設計是為了評估隨餐血糖 lispro 與基礎胰島素 NPH BID 或 insulin glargine QD, 對於病患心血管結果的影響, 總共收錄 1115 位心肌梗塞之後的病患, 實驗開始時, 有 50% 病患使用 metformin 和 SU, 單獨使用或兩個並用, 其他病患則使用胰島素做為單一治療. 追蹤2.7年後, 因為兩者沒有太大差異使得研究提早結束, 兩組對於 A1C 分別降到 7.7% VS 7.8%, 對於 cardiovascular outcomes 心血管結果的影響差異不大
cardiovascular event 心血管事件包括: 心血管死亡, 非致死性心肌梗塞, 非致死性中風, 冠狀動脈血管重建, 因急性冠心症住院)
(cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for an acute coronary syndrome).)
●The Hyperglycemia and its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus (HEART2D) trial was designed to evaluate the effects of prandial (lispro) or basal (NPH twice daily or insulin glargine once daily) insulin on cardiovascular outcomes in 1115 patients after myocardial infarction (MI) [18]. At baseline, 50 percent of the patients were taking metformin, sulfonylureas, or both, whereas the remaining patients were treated with insulin monotherapy. At a mean follow-up of 2.7 years, the trial was stopped early due to lack of efficacy. There was no difference between the prandial and basal groups in A1C (7.7 versus 7.8 percent). The cardiovascular outcomes are reviewed above.
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2023-10-25 16:08 NEJM 2001 High altitude illness 裡面沒有特別放上風險分級評估的表 NEJM 2013 Acute High Altitude Illness 下圖來自美國CDC 2024 黃皮書 下圖來自 uptodate.... -
2024-10-15 中午 11:01AM 比較必要的是丹木斯. 腸胃藥物或感冒藥物並非必備. 不過止痛藥物我覺得應該帶一些. 因為疼痛會降低行進速度. 可能會造成行程延誤. 口服類固醇也可以考慮攜帶. 外傷相關藥物(抗生素藥膏.口服抗生素)及衛材(透氣膠帶.棉棒.紗布.生理食...