Glucagon-like peptide 1 receptor agonists investigated in people with type 2 diabetes

This article compared the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to insulin in patients with type 2 diabetes (T2D). The study concluded that weekly GLP-1 RAs were more effective in controlling blood glucose, and that all GLP-1 RAs reduced weight, compared to insulin.

T2D is a progressive disease. T2D may be controlled at first by lifestyle changes and oral drugs. However, other types of medications may eventually be needed. Insulin and GLP-1 RAs are both injectable drugs used to treat T2D.

Glucagon-like peptide 1 (GLP-1) is made in the intestines and released after a meal. GLP-1 stimulates the release of insulin and inhibits the release of glucagon. These hormonal changes reduce blood glucose. GLP-1 also slows down the absorption of glucose from the intestines after a meal. GLP-1 RAs are drugs that mimic the effects of GLP-1. Some GLP-1 RAs can be taken once a week, while others are needed daily.

GLP-1 RAs have been compared to each other, and to oral diabetes drugs. However, comparisons between GLP-1 RAs and insulin are limited. 

This study analyzed the results from 11 prior studies. The participants in these studies had T2D that was not adequately controlled by oral drugs. They were treated either with a GLP-1 RA or insulin and at least one oral drug. The data that was available after 26 weeks of treatment in each study (or as close as possible to 26 weeks) was compared.

Two once-weekly GLP-1 RAs were examined; exenatide long acting release (LAR; Bydureon) and dulaglutide (Trulicity). Exenatide LAR reduced HbA1c (measures average blood glucose over the last 3 months) 0.31% more than insulin. Dulaglutide reduced HbA1c 0.39% more than insulin. Two other GLP-1 RAs were examined; twice-daily exenatide (Byetta), and once-daily liraglutide (Victoza). The daily GLP-1 RAs did not reduce HbA1c significantly more than insulin.

All of the GLP-1 RAs reduced body weight more than insulin. The daily GLP-1 RAs reduced weight more than the weekly GLP-1 RAs. The risk of a hypoglycemic event  (dangerously low blood glucose) was 68% lower for participants treated with exenatide LAR than for participants treated with insulin. Participants who were treated with liraglutide had a 60% lower risk of a hypoglycemic event than those treated with insulin.  

The authors concluded that once-weekly GLP-1 RAs are effective in reducing HbA1c and all GLP-1 RAs are effective in reducing weight, compared to insulin. Some GLP-1 RAs might have a lower risk of hypoglycemic episodes than insulin. 

Different studies defined hypoglycemic events differently, and this could impact the results.

Non-obese patients, non-Caucasian patients, and female patients were underrepresented in this article. As such, the results may not apply equally to all patients with T2D. The patients in the studies were using different types of oral drugs. These drugs all have different effects that may have influenced the results. Several other types of GLP-RAs exist that were not included in the study. These drugs may have different effects than the ones in the study.

Several of the authors were connected with Eli Lilly. This company manufactures dulaglutide. 

Discuss the effects of GLP-1 RAs with your physician.