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