Basal Insulin Analogs for Type 2 Diabetes Are Similar in Efficacy

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Neutral protamine lispro was associated with a higher risk for hypoglycemia than other insulin regimens.
Neutral protamine lispro was associated with a higher risk for hypoglycemia than other insulin regimens.

Currently available basal insulin analogs for type 2 diabetes (T2D) are not substantially different in their ability to lower glucose, but this conclusion is based primarily on low-quality indirect evidence, according to a new meta-analysis published in the Annals of Internal Medicine.

Conclusive evidence about the comparative safety and efficacy of the new generation of long-acting insulin analogs is lacking, as they have primarily been compared with insulin glargine. In the absence of adequate data on direct comparisons between the agents, investigators conducted a systematic review and meta-analysis to assess the comparative efficacy and safety of these agents.

The final analysis included 39 randomized clinical trials that lasted at least for 12 weeks, with a total patient population of 26,195. Ten basal insulin analogs were assessed. Overall, differences in glycemic efficacy among the various agents were minimal and probably lacked clinical significance. They found that degludec (Deg-3TW) was inferior to most of the other regimens for reducing HbA1c levels, with mean differences that ranged from 0.21% (vs degludec100 U/mL [Deg-100]) to 0.32% (vs glargine 300 U/mL [Glar-300]), although the evidence was low to very-low quality.

High-to-moderate quality evidence showed that detemir had a favorable weight profile vs all other agents, with weighted mean differences that ranged from -0.68 kg (vs Glar-300) to -1.76 kg (vs LY2963016). Less weight gain was seen with Glar-300 vs glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence also showed that Deg-100, Deg-200, and Glar-300 were associated with a lower incidence of nocturnal hypoglycemia vs detemir, Glar-100, and LY2963016.

“In addition to short-term efficacy and safety, effects of individual drugs on long-term cardiovascular outcomes and cost-effectiveness data should be considered for optimal therapeutic decision making,” wrote the investigators.

Reference

Madenidou AV, Paschos P, Karagiannis T, et al. Comparative benefits and harms of basal insulin analogues for type 2 diabetes: a systematic review and network meta-analysis [published online July 10, 2018]. Ann Intern Med. doi: 10.7326/M18-0443

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