Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes

Abstract

Objective: To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes. Methods:After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c ≥7.5% and ≤11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24.Results: Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs.8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m 2 ), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level <7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group. Conclusion:In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes.

Improved Glucose Control With Weight Loss, Lower Insulin Doses, and No Increased Hypoglycemia With Empagliflozin Added to Titrated Multiple Daily Injections of Insulin in Obese Inadequately Controlled Type 2 Diabetes

“…In a stable MDI insulin period during the first 18 weeks, empagliflozin resulted in significant HbA 1c reduction and weight loss compared with placebo, with a slightly increased frequency of mild hypoglycemic events but no increase in severe hypoglycemic events. An increased frequency of hypoglycemia has previously been reported when antidiabetes agents with a low risk of hypoglycemia are added to insulin (17,18). Of note, over the full 52-week treatment period, including the treatto-target period, the proportion of patients with confirmed hypoglycemic AEs was similar in all treatment groups.…”

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

“…96 Data concerning the glycemic benefits of incretin-based therapy combined with basal insulin are accumulating; combination with GLP-1 receptor agonists may be helpful in some patients. 97,98 Once again, the costs of these more elaborate combined regimens must be carefully considered.…”

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

“…Therefore, it may also be possible to speculate on the clinical efficacy of combining a DPP-4 inhibitor with insulin. Four placebo-controlled trials have investigated the clinical efficacy and safety of adding a DPP-4 inhibitor to a basal insulin regimen (with or without metformin or SU; Table 4) [66][67][68][69]. All studies reported consistent results, with a reduction in HbA 1c levels of 0.5-0.6% on average if daily insulin dosages were maintained unchanged.…”