Impact of GLP-1 agonists in postprandial hypoglycemia after bariatric surgery inconclusive
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GLP-1 receptor agonists may reduce the number of postprandial hypoglycemia episodes after bariatric surgery, but more research is needed to guide use in practice, according to a systematic review published in Obesity.
“Treatment for hyperinsulinemic hypoglycemia syndrome following bariatric surgery includes various dietary, medical and surgical interventions, but these are not always successful in reducing hypoglycemic episodes,” Georgios K. Dimitriadis, MD, PhD, MRCP, MSc, consultant and senior lecturer of endocrinology and obesity medicine at the King’s College Hospital NHS Foundation Trust, U.K., and colleagues wrote. “Therefore, alternative treatments must be considered. Although the use of GLP-1 receptor agonists appears counterintuitive, early research has suggested that it could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability. We have performed the first systematic review, to our knowledge, of the literature, and although there is some evidence to support the use of GLP-1 receptor agonists in late-stage dumping syndrome, further work is required to determine an ideal position in the therapeutic algorithm for this class of drugs.”
Researchers conducted a systematic review of the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Scopus databases for studies analyzing the impact of GLP-1 receptor agonists on postprandial hypoglycemia for adults who undergo bariatric surgery. Study description, patient-reported outcomes and quality of life, adverse events and the number of hypoglycemia events were collected. The primary outcomes were the reduction in hypoglycemia events in participants and improvement hypoglycemia symptoms with use of GLP-1 receptor agonists.
The researchers found only five published papers on the topic, along with one clinical trial that had been completed but had not yet published results. Of the five published studies, three were randomized controlled trials, one was a case report of one patient, and one was a case series of five patients. The five studies combined included only 30 participants. A meta-analysis was unable to be performed due to differences in the studies and missing data.
Findings were mixed among the five studies included in the review. In the case series of five adults, the researchers found GLP-1 receptor agonists were protective of symptomatic postprandial hypoglycemia in all participants. In the other case report, a patient in China who had hypoglycemia after bariatric surgery experienced an improvement in hypoglycemia episodes with 1 month of twice-daily beinaglutide.
In one randomized controlled trial, which included 18 adults who had postprandial hypoglycemia after Roux-en-Y gastric bypass surgery, only one participant used a GLP-1 receptor agonist. The researchers reported the adult had an improvement on the frequency of postprandial hypoglycemia. Another randomized controlled trial compared five different treatments in adults experiencing postprandial hypoglycemia after surgery, with one of the treatments being 1.2 mg liraglutide (Victoza, Novo Nordisk). The researchers found liraglutide did not reduce the number of hypoglycemic episodes or postprandial insulin concentrations. In the final randomized controlled trial, researchers used a hyperinsulinemic-hypoglycemic clamp technique on two occasions: once with an infusion of exenatide (Byetta/Bydureon, AstraZeneca) and the other occurrence with saline. The researchers found no plasma glucose-raising effect or changes in glucagon with exenatide, and although hypoglycemia episodes did not increase, symptoms were not altered.
“The evidence into a GLP-1 mechanism of action in the context of postprandial hypoglycemia is currently inconclusive,” the researchers wrote. “GLP-1 receptor agonists did not appear to reverse an episode of hypoglycemia by counterregulatory hormonal and metabolic responses during a fasting state, but it is more likely that they work by preventing an episode occurring when patients are eating. There is some evidence that the insulin and glucose peaks are synchronous when taking GLP-1 receptor agonists. Based only on very limited data, there appears to be less variability of GLP-1 release, which prevents excessive peaks of endogenous insulin and, ultimately, postprandial hypoglycemia. Whether this happens via continuous stimulation of the GLP-1 receptor is not known.”
The researchers said future studies need to consider each participant’s diet, whether they have symptomatic postprandial hypoglycemia and the length of follow-up on treatment.
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