The long-term glycemic effects of glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes mellitus (T2DM) remain uncertain despite growing interest in incretin-based therapies. A randomized placebo-controlled trial published in The Lancet Diabetes & Endocrinology evaluated whether continuous subcutaneous GIP infusion alone or combined with semaglutide improved glycemic control in adults with T2DM.
The single-center, double-blind trial enrolled adults aged 18 to 74 years with T2DM, glycated hemoglobin (HbA1c) levels of 6.5% to 10.5%, and body mass index (BMI) of 25 to 50 kg/m². Participants were randomized to placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP.
After an 8-week semaglutide or placebo run-in period, participants continued treatment for an additional 6 weeks with continuous subcutaneous GIP or placebo infusion. The primary endpoint was change in 14-day mean glucose concentration measured by continuous glucose monitoring at week 14.
Findings
- The study randomized 61 participants, including 15 assigned to placebo plus placebo, 16 to placebo plus GIP, 15 to semaglutide plus placebo, and 15 to semaglutide plus GIP.
- The estimated effect of GIP on change in 14-day mean sensor-detected glucose was 0.80 mmol/L (97.5% confidence interval [CI], –0.18 to 1.80; P = 0.13) for placebo plus GIP versus placebo plus placebo.
- Addition of GIP to semaglutide did not significantly change mean glucose levels compared with semaglutide alone (estimated effect, 0.05 mmol/L; 97.5% CI, –0.85 to 0.95; P = 1.00).
- Injection site reactions were the most common adverse events and occurred in 22 participants (36%).
- Gastrointestinal adverse events were more frequent in semaglutide-treated groups, occurring in 73% of the semaglutide plus placebo group and 80% of the semaglutide plus GIP group.
Six weeks of subcutaneous GIP infusion did not significantly improve glycemic control in adults with T2D when used alone or in combination with semaglutide. Interpretation of placebo plus GIP findings remained limited because of study discontinuations.
