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How do the effectiveness and safety of long-acting GLP-1 RAs compare to short-acting GLP-1 RAs, when paired with basal insulin?
Glucose-like peptide 1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes patients. They are known to decrease weight effectively, have a low risk of hypoglycemia, and to lower HbA1c levels. Recent trials suggest that long-acting GLP-1 RAs have an increased benefit over the short-acting GLP-1 RAs in patients that have type 2 diabetes, and were shown to reduce HbA1c, weight, fasting plasma glucose, and enhance safety profile and decrease side effects such as vomiting and nausea.
Meta-analysis indicates that long-acting GLP-1 RAs should be used in conjunction with basal insulin, long-acting insulin. Basal insulin aids in managing blood sugar at night and between meals. Long-acting GLP-1 receptor agonists are known to delay the stomach’s emptying, suppress post glucagon secretion, and increase insulin sensitivity. The duo has improved glycemic control, effectively enhanced fasting glucose concentrations, and lowered weight in patients better than the short-acting GLP-1 RAs combined with basal insulin. The combination also showed a better adverse effect profile concerning gastrointestinal effects.
The study aimed to compare the efficacy and safety of long-acting GLP-1 RAs with basal insulin to short-acting GLP-1 RAs in patients who have type 2 diabetes. The trials were open-label, blinded, randomized control trials. The study selection was based upon a PubMed search. Articles selected were the clinical trials that compared GLP-1 receptor agonist inhibitors combined with basal insulin versus basal insulin with or without the placebo present. During the selection, studies were included if they were published before December 31, 2018. Of those studies, 14 publications were used. Within these reports, 8 of them showed short-acting GLP-1 RAs being studied and 6 of the reports showed long-acting GLP-1 RAs with basal insulin. The quality of the study was assessed by using the data score and Risk of Bias tool.
Studies that included baseline and HbA1c results from the end of the trial, fasting plasma glucose levels, weight, and patients discontinuing treatment before the trial ended were included. The minimum duration of the treatment was reported to be six weeks. The primary endpoints were as follows: HbA1c levels reduced significantly, alterations in goal levels of HbA1c less than 7%, weight reduction using basal insulin versus basal insulin with or without the placebo present, and fasting glucose in most of the studies. The safety endpoints were adverse effects, early discontinuation of therapy, and a lower risk of hypoglycemia.
The analysis of the results found that long-acting GLP-1 RAs were more effective than short acting in reduction of HbA1c (95% confidence interval; P=0.007; -6 mmol/mol), fasting plasma glucose (-0.7 mmol/mol’ P=0.007; 95% confidence interval), and weight ( -1.4 kg; -2.2 to 0.6; P=0.002). The safety endpoint for patients receiving long-acting GLP-1 RAs showed a 52% decrease in nausea with a P-value of <0.0001, and vomiting showed a 36% decrease with a P-value of 0.0002 (Campbell). Both long- and short-acting GLP-1 RAs improved HbA1c and lowered weight in patients when combined with basal insulin.
The study mentioned that publication bias could have occurred, but it did not significantly impact the results. There was a lack of HbA1C variation in patients taking short-acting GLP-1 RAs versus long-acting. There were noted limitations of the trials. First, there was a small number of publications available. There were differences in the GLP-1 RAs compounds used and diverse protocols used in the trials.
In conclusion, long-acting GLP-1 RAs should be used in conjunction with basal insulin to yield adequate results. They have been shown to improve glycemic control, decrease weight, and improve fasting plasma glucose concentration. They have also been shown to have a benefit in reducing the gastrointestinal profile regarding adverse effects.
Practice Pearls:
- Long-acting glucose-like peptide 1 receptor agonists combined with basal insulin is considered beneficial in patients with type 2 diabetes.
- Glycemic control was improved using long-acting, when compared to short-acting, GLP-1 RAs.
- Long-acting GLP-1 RAs with basal insulin showed less vomiting and nausea would occur when compared to basal insulin with or without the placebo present.
Campbell, Patrick. “Long-Acting GLP-1 RAs More Effective than Short-Acting for Diabetes Management.” Endocrinology Network, August 28, 2020.
“Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-Analysis.” Diabetes Care, American Diabetes Association, September 1, 2020.