GLP-1 Analog Counteracts Antipsychotic-Induced Glucose Intolerance, Weight Gain

Interventions seeking to counteract antipsychotic-induced weight gain and cardiometabolic disturbances have had limited success.

This article is part of Endocrinology Advisor’s coverage of the American Diabetes Association’s 77th Scientific Sessions (ADA 2017), taking place in San Diego, CA. Our staff will report on medical research and technological advances in diabetes and diabetes education, conducted by experts in the field. Check back regularly for more news from ADA 2017.

Liraglutide significantly improved glucose tolerance, body weight, and other cardiometabolic disturbances in clozapine- or olanzapine-treated patients who have disorders on the schizophrenia spectrum, according to research presented at the American Diabetes Association 77th Scientific Sessions, held June 9-13 in San Diego, California.

Although patients with schizophrenia have higher mortality rates compared with the background population (primarily caused by cardiovascular disease), interventions seeking to counteract antipsychotic-induced weight gain and cardiometabolic disturbances have had limited success. As a result, Louise Vedtofte, of Gentofte Hospital, Københavns Universitet, in Copenhagen, Denmark, and colleagues investigated the effects of glucagon-like peptide-1 liraglutide in obese/overweight patients with prediabetes and schizophrenia spectrum disorders on stable treatment with clozapine or olanzapine.

In a 16-week, placebo-controlled double-blind trial of 103 patients randomly divided into comparable groups, the researchers gave 1.8 mg/d of liraglutide to participants (6 dropped out). Glucose tolerance improved with liraglutide (P <.001) compared with no change with placebo (P =.95; between group P <.001).

In the liraglutide-treated group, 63.8% of the participants developed normal glucose tolerance compared with 16.0% of the placebo-treated participants (P <.001; number-needed-to-treat=2). Body weight decreased with liraglutide (-4.7±0.5 kg) and increased with placebo (+0.5±0.7 kg; P <.001).1

Other results confirmed that liraglutide was well tolerated as well: reductions in waist circumference (-4.0±0.6 vs 0.5±0.7 cm; P <.001), systolic blood pressure (-1.4±2.0 vs 1.1±1.8 mm Hg; P =.04), visceral fat (-315.8±75.3 vs -24.0±41.7 g; P =.02), and low-density lipoprotein cholesterol (-0.4±0.08 vs -0.06±0.05 mmol/L; P <.001) were significantly greater with liraglutide compared with placebo. Adverse events with liraglutide were primarily gastrointestinal, and serious adverse events were significantly lower in the liraglutide-treated group (12% vs 26%; P =.04).

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Vedtofte L, Larsen JR, Jakobsen MSL, et al. The GLP-1 analog liraglutide improves glucose tolerance and reduces body weight in schizophrenia spectrum disorder patients treated with clozapine or olanzapine. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego, CA. Abstract 129-OR.