Gemigliptin-metformin combo leads to better glycemic control without hypoglycemia risk

"In our randomized controlled trial (RCT) of drug-naïve Korean patients with type 2 diabetes, 77% of the patients given the gemigliptin–metformin therapy achieved the target goal of HbA1c ≤ 7.0% (53 mmol/mol)," the researchers wrote in their study published in the journal Nutrients. They explained, "this approach favourably changed the amino acid levels and gut microbiota, indicating potential improvements in anti-inflammatory effects and pancreatic β-cell function."

"Our findings indicate that changes in the gut microbiota are critical for augmenting the efficacy of gemigliptin therapy. This may apply to DPP-4 inhibitors in more general terms."

Changes in humans' gut microbiota can impact the safety and efficacy of medications. Among anti-diabetic drugs, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors (DPPi) might affect the gut microbiome related to glucose metabolism. Soo Lim from Seoul National University College of Medicine in Seongnam, Republic of Korea, and colleagues conducted a randomized, controlled, active-competitor study to compare the effects of gemigliptin–metformin versus glimepiride–metformin combinations as initial therapies on glucose homeostasis and gut microbiota in drug-naive patients with type 2 diabetes.

Alterations in gut microbiota, amino acid blood levels, body composition, and biomarkers linked to glucose regulation were investigated. The study included seventy drug-naïve patients with type 2 diabetes (mean age, 52.2 years) with an HbA1c (glycated hemoglobin) level of ≥7.5%. They were assigned to either combination of glimepiride–metformin or gemigliptin–metformin therapies for 24 weeks.

The study led to the following findings:

• Although both treatments decreased the HbA1c levels significantly, the gemigliptin–metformin group achieved HbA1c ≤ 7.0% without hypoglycemia or weight gain more effectively than the glimepiride–metformin group (59% vs. 24%).
• At the phylum level, the Firmicutes/Bacteroidetes ratio tended to decrease after gemigliptin–metformin therapy, with a significant depletion of taxa belonging to Firmicutes, including Lactobacillus, Ruminococcus torques, and Streptococcus.
• Regardless of the treatment modality, a distinct difference in the overall gut microbiome composition was noted between patients who reached the HbA1c target goal and those who did not.

To conclude, patients with type 2 diabetes treated with gemigliptin–metformin significantly achieved the glycemic target without hypoglycemia or weight gain, better than with glimepiride–metformin; these improvements might be linked with the beneficial changes in gut microbiota.

Reference:

Lim, S.; Sohn, M.; Florez, J.C.; Nauck, M.A.; Ahn, J. Effects of Initial Combinations of Gemigliptin Plus Metformin Compared with Glimepiride Plus Metformin on Gut Microbiota and Glucose Regulation in Obese Patients with Type 2 Diabetes: The INTESTINE Study. Nutrients 2023, 15, 248. https://doi.org/10.3390/nu15010248