lc15-0444 and glimepiride

The efficacy and safety of medications can be affected by alterations in gut microbiota in human beings. Among antidiabetic medications, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors might affect gut microbiomes, which are related to glucose metabolism. This was a randomized, controlled, active-competitor study that aimed to compare the effects of combinations of gemigliptin−metformin vs. glimepiride−metformin as initial therapies on gut microbiota and glucose homeostasis in drug-naïve patients with type 2 diabetes. Seventy drug-naïve patients with type 2 diabetes (mean age, 52.2 years) with a glycated hemoglobin (HbA1c) level ≥7.5% were assigned to either gemigliptin−metformin or glimepiride−metformin combination therapies for 24 weeks. Changes in gut microbiota, biomarkers linked to glucose regulation, body composition, and amino acid blood levels were investigated. Although both treatments decreased the HbA1c levels significantly, the gemigliptin−metformin group achieved HbA1c ≤ 7.0% without hypoglycemia or weight gain more effectively than did the glimepiride−metformin group (59% vs. 24%; p < 0.05). At the phylum level, the Firmicutes/Bacteroidetes ratio tended to decrease after gemigliptin−metformin therapy (p = 0.065), with a notable depletion of taxa belonging to Firmicutes, including Lactobacillus, Ruminococcus torques, and Streptococcus (all p < 0.05). However, 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 (p < 0.001). Treatment with gemigliptin−metformin resulted in a higher achievement of the glycemic target without hypoglycemia or weight gain, better than with glimepiride−metformin; these improvements might be related to beneficial changes in gut microbiota.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Gastrointestinal Microbiome; Glucose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Intestines; Metformin; Middle Aged; Obesity; Treatment Outcome; Weight Gain

To investigate the effects of gemigliptin on cardiac function and compare the effects of gemigliptin and glimepiride in patients with type 2 diabetes (T2D).. Sixty T2D patients being treated with metformin were assigned to a gemigliptin group (50 mg daily) or a glimepiride group (2 mg daily) for 24 weeks. The preadjudicated extension period was up to 52 weeks. Glucose metabolism variables and cardiac biomarkers were measured. Echocardiography was used to evaluate cardiac functions.. The HbA1c levels decreased significantly from 8.1% ± 0.6% to 6.8% ± 0.6% in the gemigliptin group and from 8.1% ± 0.6% to 7.0% ± 0.7% in the glimepiride group, without a between-group difference. Gemigliptin reduced insulin resistance, high sensitivity C-reactive protein and low-density lipoprotein cholesterol levels, and blood pressure, and increased adiponectin level compared with glimepiride therapy. Gemigliptin induced favourable changes in body composition. Left ventricular end-diastolic volume decreased in the gemigliptin group but increased in the glimepiride group, with a borderline between-group difference. Cardiac biomarkers did not change significantly in either group. At 52 weeks, the HbA1c levels in both groups increased slightly; 7.3% ± 0.8% in the gemigliptin group versus 7.7% ± 1.3% in the glimepiride group, without a between-group difference.. Gemigliptin had a comparable glucose-lowering efficacy without deleterious effects on cardiac functions or on biomarkers reflective of myocardial injury or heart failure during the 24-week observation period. However, larger, longer-term studies are needed to confirm these findings.

Topics: Aged; Diabetes Mellitus, Type 2; Echocardiography; Female; Heart; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Piperidones; Prospective Studies; Pyrimidines; Sulfonylurea Compounds

The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase-4 (DPP-4) inhibition in patients with type 2 diabetes. This multicentre, randomized, active-controlled, open-label exploratory study included 69 patients with HbA1c > 7.5%. Subjects were randomized to receive gemigliptin 50 mg (n = 24), sitagliptin 100 mg (n = 23) or glimepiride 2 mg (n = 22) for 12 weeks. After 12 weeks, the change in mean amplitude of glycaemic excursion (MAGE) compared with baseline was significantly lower in the DPP-4 inhibitor groups compared with that in patients who received glimepiride. Furthermore, the standard deviation (SD) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride. The DPP-4 inhibition was significantly correlated with changes in MAGE and SD of glucose. In conclusion, gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes, and the DPP-4 inhibition was associated with a reduction in glycaemic variability.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Piperidones; Pyrimidines; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Young Adult

Gemigliptin is approved for the treatment of type II diabetes mellitus. Sulfonylureas are commonly used in combination with other antidiabetic drugs to improve glycemic control. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of gemigliptin and glimepiride combination therapy compared with those of monotherapies.. A randomized, open-label, crossover study was performed on healthy Korean male volunteers. Each subject received the following treatments (A and B) with a 7-day washout period: treatment A consisted of gemigliptin 50 mg once daily administered orally for 6 days, followed by concomitant oral dosing of glimepiride 4 mg and gemigliptin 50 mg on day 7; treatment B consisted of a single dose of glimepiride 4 mg. Blood samples were collected up to 24-h postdose on day 6 (gemigliptin) and day 7 (gemigliptin and glimepiride) following treatment A, and on day 1 (glimepiride) following treatment B. Concentrations of gemigliptin, glimepiride, and metabolites were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Safety assessments were performed throughout the study.. Twenty-three subjects completed the study. The geometric mean ratios (GMRs) of C max,ss and AUC τ,ss for gemigliptin were 1.0097 [90 % confidence interval (CI) 0.924-1.103] and 0.9997 (90 % CI 0.976-1.024), respectively. For glimepiride, the GMRs of C max and AUClast were 1.031 (90 % CI 0.908-1.172) and 0.995 (90 % CI 0.902-1.097), respectively. Both combination and monotherapy were well tolerated, and no serious adverse events were reported.. Gemigliptin and glimepiride did not alter the pharmacokinetic properties of each other when they were co-administered in healthy volunteers, and were generally tolerated.

Topics: Administration, Oral; Adult; Area Under Curve; Asian People; Chromatography, Liquid; Cross-Over Studies; Drug Interactions; Humans; Hypoglycemic Agents; Male; Piperidones; Pyrimidines; Republic of Korea; Sulfonylurea Compounds; Tandem Mass Spectrometry; Young Adult