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GLP-1 Receptor Agonist for Type 1’s

Besides lowering A1c, study finds success with using less insulin and weight reduction.

Type 1 diabetes (T1DM) is a disease characterized by autoimmune mediated destruction of the insulin-producing beta cells of endocrine pancreas. Beside insulin deficiency, T1DM is also characterized by abnormal suppression of glucagon secretion in response to hyperglycemia. All these abnormalities are likely to leave patients dependent upon exogenous insulin administration for survival. GLP-1 is a hormone secreted by L-cells of distal small intestine and colon. GLP-1 exerts its effects through the interaction with GLP-1 receptor expressed in the pancreatic islets, lung, hypothalamus, stomach, heart, and kidney. It belongs to the group of incretin peptides and it stimulates insulin and inhibits glucagon secretion. Actions of GLP-1 also include delaying of gastric emptying, reduction of appetite, and induction of satiety. On the other hand, evidences have indicated the role of GLP-1 in increasing beta cell proliferation and differentiation and in decreasing the rate of beta cell apoptosis in animals. GLP-1 receptor agonists are approved for type 2 patients, however, they are still not approved for use in T1DM, although they could have beneficial effects in both new onset and longstanding T1DM patients, mainly as an adjunctive therapy to insulin in order to improve glycemic control and body weight management in longstanding disease or to reduce insulin requirements or even to delay the absolute dependence upon insulin administration in new onset T1DM. Even reducing the amount of insulin needed, can help to reduce A1c outcomes.

People with type 1 diabetes experienced improvements in HbA1c levels after liraglutide treatment, according to a study presented at the AACE meeting in Austin, TX.

Led by Raju Panta, MD, of the State University of New York at Buffalo, the review and meta-analysis reported that after type 1 diabetes patients were treated with liraglutide (Victoza and Saxenda) for 12 weeks, they experienced a 0.29% reduction in HbA1c levels versus placebo.

This was the first systematic review and meta-analysis of the literature regarding Glucagon like peptide-1 receptor agonists (GLP-1RA) for the treatment of individuals with type 1 diabetes,

Panta, in his presentation, added that currently only agents approved for use in patients with type 1 diabetes mellitus are multiple-dose insulin injections, continuous subcutaneous insulin infusion, and pramlintide. “Despite the advances in treatment of patients with type 1 diabetes,” he said, “with availability and use of self-monitoring of blood glucose and improved methods of insulin delivery like insulin pens and insulin pumps, many patients with type 1 diabetes do not achieve the target HbA1c.”

Panta explained that his group aimed to pool the data from prior phase III trials in order to isolate safety and efficacy outcomes for this specific patient population. They utilized a random-effects model to primarily measure total change in A1c levels, body weight, basal insulin, bolus insulin, as well as adverse events with use of GLP-1 receptor agonist therapy in patients with type 1 diabetes.

Following a search of literature from research databases, including Cochrane Central, PubMed, and Embase, a total of 212 individuals with type 1 diabetes were included in the final analysis. These participants were drawn from three randomized controlled trials, which included liraglutide.

 

In addition to a reduction in A1c levels, the researchers reported significant improvements across all primary outcomes assessed. Liraglutide use for type 1 diabetes for 12 weeks was associated with a 4.39 unit reduction in daily bolus insulin, as well as a 2.55 drop in daily basal insulin. Similarly, patients explained that the extent of the reduction within 3 months time was quite surprising.

The reduction of HbA1c liraglutide group was modest (0.29%) when compared with placebo, but was statistically significant. “As patients with type 1 diabetes mellitus do not have functional beta cells, we hypothesize that the reduction in HbA1c was mostly mediated via reduction in postprandial glucagon (secreted by alpha cells) in the liraglutide group.”

However, in terms of adverse outcomes, liraglutide use was associated with a significant increase in nausea when compared to placebo, although it did not significantly increase prevalence of vomiting.

The group suggested these findings may be attributed to the reduction in postprandial glucagon surge following appetite suppression induced by liraglutide, due to the lack of functioning beta cells in those with type 1 diabetes.

In another study, even back to 2013, clinicians and patients are rapidly adapting GLP-1 receptor agonists as efficacious and safe therapeutic options for managing type 2 diabetes (T2DM). GLP-1 receptor agonists stimulate insulin production and secretion from the pancreatic β cells in a glucose-dependent manner, improve gastric emptying, favor weight reduction, and reduce post-absorptive glucagon secretion from pancreatic α cells. GLP-1 receptor activity is impaired in patients with T2DM. GLP-1 secretion and subsequent physiologic actions in patients with type 1 diabetes is ill-defined. Some researchers have suggested that the use of GLP-1 receptor agonists in T1DM may reduce excessive postprandial glucagon secretion allowing patients to reduce their total daily dose of exogenous insulin. Hypoglycemia risk may also be minimized in T1DM as glucagon counter-regulation can be preserved to some degree via the glucose-dependent action of the GLP-1 receptor agonists.

Practice Pearls

  • Researchers reported significant improvements across all primary outcomes assessed for GLP-1 receptor agonists.
  • Hypoglycemia risk may also be minimized in T1DM with the use of a GLP-1 receptor agonists.
  • Use for type 1 diabetes for 12 weeks was associated with a 4.39 unit reduction in daily bolus insulin, as well as a 2.55 drop in daily basal insulin.

AACE 2017; Source Reference: Panta R, et al “A Systematic review and meta-analysis of randomized controlled trials in use of GLP1 receptor agonists in type 1 diabetes mellitus” AACE 2017; Abstract 216.

 

Curr Diab Rep. 2013 Oct;13(5):663-8. doi: 10.1007/s11892-013-0404-x.  http://www.diabetesincontrol.com/diabetes-therapies/glp-1/