4. Discussion
obesity, hyperhomocysteinemia, hypoglycemia, weight gain, gemigliptin-based, HbA1c ≤, type 2 diabetes
OBESITY, HYPERHOMOCYSTEINEMIA, HYPOGLYCEMIA, INSULIN RESISTANCE, TYPE 2 DIABETES
In this RCT, the proportion of participants with HbA1c ≤ 7.0% (53 mmol/mol) but lacking hypoglycemia was significantly greater in the gemigliptin–metformin combination group compared with the glimepiride–metformin combination group. In addition, the proportion of participants who achieved this goal without hypoglycemia or weight gain was more than double in the gemigliptin–metformin combination group vs. the glimepiride–metformin combination group. This outcome suggests that an early combination of gemigliptin–metformin is preferable and safer for the treatment of drug-naïve patients with type 2 diabetes with moderately high HbA1c levels.Of note, the initial combination treatment of gemigliptin–metformin increased the abundance of the gut microbiota associated with improvements in glucose regulation and reduced body fat. At the phylum level, the Firmicutes and Firmicutes/Bacteroidetes bacteria, which are markers that are well known to be linked to obesity [In this study, a better glycemic control was associated with several genera of gut microbiota: with high abundance of the Here, weight gain in the study participants was associated with Intriguingly, the two therapies altered the gut microbiota in different ways in this study, which might contribute to better glucose control in the gemigliptin-based therapy. Conversely, the glimepiride–metformin therapy decreased In the estimated microbial functional analysis, gemigliptin-based therapy altered several metabolic pathways (Moreover, several studies have shown that metformin changes the gut microbiota favorably such as increasing the abundance of In the amino acid analysis, serum methionine levels were decreased after both treatments. A high methionine level is associated with hyperhomocysteinemia and insulin resistance [Increased AAA levels, particularly tyrosine, are associated with insulin resistance and obesity [In this study, the proinsulin/insulin ratio decreased significantly after gemigliptin–based therapy, but not after glimepiride–metformin therapy. The change from proinsulin to insulin is a critical process in pancreatic β-cells for glucose regulation [Therapy with DPP-4 inhibitors improves glycemic control with a similar efficacy as that of sulfonylureas; however, they do not induce hypoglycemia or weight gain [Gemigliptin has several advantages over other glucose-lowering agents. It was more effective than glimepiride in reducing glycemic variability as an initial combination therapy with metformin in patients with type 2 diabetes [In this RCT of drug-naïve Korean patients with type 2 diabetes, 77% of the participants who received the gemigliptin–metformin combination therapy achieved the glycemic target goal of HbA1c ≤ 7.0% (53 mmol/mol) without hypoglycemia. This approach altered the gut microbiota and amino acid levels favorably, suggesting potential improvements in pancreatic β-cell function and anti-inflammatory effects. Our findings suggest that changes in the gut microbiota play important roles in augmenting the efficacy of gemigliptin therapy. This may apply to DPP-4 inhibitors in more general terms.