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Liraglutide (Victoza) Provides Good Control with Less Hypoglycemia for MODY

Besides sulfonylureas, GLP-1RA can also be a treatment option for HNF1A diabetic patients….

Maturity-onset diabetes of the young adults (MODY) is responsible for 1-2% of all cases of diabetes. HNF1A diabetes is caused by loss of B-cell functions. It is usually misclassified as type 1 diabetes due to common hyperglycemic symptoms such as polyuria and polydipsia. Most of the patients with HNF1a have mutation in the hepatocyte nuclear factor 1a, HNF1A or MODY3. Patients with HNF1A are usually treated with sulfonylureas.

From September 2012 to August 2013, researchers conducted a randomized, double-blinded, cross over trial, comparing the glucose-lowering effects and risk of hypoglycemia of sulfonylureas and GLP-1 receptor agonists in patients with HNF1A diabetes. They studied sixteen patients, 8 women and 8 men, of age 23-67 years with HNF1A diabetes. All patients were randomized to receive treatment of either a once-daily injection of liraglutide and placebo tablets, or a once-daily tablet of glimepiride and once-daily injection of placebo for 6 weeks. The primary endpoint was FPG after 6 weeks of treatment. The secondary endpoints were episodes of hypoglycemia, serum fructosamine, response to insulin, C-peptide, and glucagon, and growth hormones following a test meal combined with 30 minutes of bicycle test.

Glimepiride (P=0.003) decreased FPG more effectively than liraglutide (P=0.012), but without any significant difference (P=0.624). Both medicines lowered plasma glucose level without any significant difference, P= 0.121. Total of eight episodes of hypoglycemia occurred while on glimepiride compared to one episode while on liraglutide.

The study results showed that both glimepiride and liraglutide reduced FPG and glimepiride showed almost 10 fold higher risk of mild hypoglycemia compared to liraglutide. Overall, GLP-1RAs could be another treatment option for HNF1A diabetes, especially when hypoglycemia is an issue. But, individualized therapy should be considered depending on the glucose lowering effects, adverse effects, method of administration, and cost.

Practice Pearls:

  • This study looked at episodes of mild hypoglycemic when patients were taking glimepiride and liraglutide.
  • Glimepiride showed effective decreased in FPG compared to glimepiride but without significant difference.
  • Liraglutide showed less hypoglycemic episodes compared to glimepiride.

Ostoft SH, et al “Glucose-lowering effects and low risk of hypoglycemia in patients with maturity-onset diabetes of the young when treated with a GLP-1 receptor agonist: A double- blind, randomized, crossover trial” Diabetes Care 2014; DOI: 10.2337/dc13-3007.