BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

OBJECTIVE: To observe the clinical efficacy of sitagliptin plus insulin on patients with brittle diabetes and to determine the effect of the combined therapy on glucagon secretion.
 METHODS: This randomized, double-blinded and placebo-controlled trial included 30 patients with brittle diabetes. Participants were randomly assigned (1:1) to receive the treatment of either sitagliptin plus insulin or placebo plus insulin for 12 weeks. The blood glucose, hemoglobin A1c, insulin dose, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and other parameters were determined.
 RESULTS: After 12 weeks of treatment, blood glucose was controlled better by sitagliptin plus insulin (P<0.01). The patients had significantly lower glucose variability indices, lower daily insulin requirement and hemoglobin A1c in the group of sitagliptin plus insulin (P<0.01). After steamed bun test, past-meal GLP-1 levels at 30 min were higher (P<0.01) while GIP levels were lower (P<0.01), with glucagon suppression in the sitagliptin plus insulin group. No significant change was observed at any time point in placebo plus insulin group.
 CONCLUSION Sitagliptin significantly decreases blood glucose level and blood glucose fluctuation, which may contribute to the ability of sitagliptin in decreasing glucagon secretion.
Blood Glucose ; analysis ; C-Peptide ; blood ; Diabetes Mellitus, Type 1 ; drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; Double-Blind Method ; Drug Therapy, Combination ; Gastric Inhibitory Polypeptide ; blood ; Glucagon ; blood ; Glucagon-Like Peptide 1 ; blood ; Glycated Hemoglobin A ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; therapeutic use ; Insulin ; administration & dosage ; therapeutic use ; Sitagliptin Phosphate ; administration & dosage ; therapeutic use

BACKGROUNDDipeptidyl peptidase-IV (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes. However, their effects on hepatic glucose production (HGP) in obesity are not clear. This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity.

METHODSSprague Dawley male rats were divided into four groups, each on a different diet: general rat chow, n = 10 (G); G + sitagliptin, n = 10; high fat chow (obesity), n = 10 (55% fat calories, HFO); HFO + sitagliptin, n = 10. After 10 weeks, the rats were fasted overnight and glucose metabolism was determined using 3-(3)H-glucose and (14)C-glycerol as tracers.

RESULTSGlycerol rate of appearance (P < 0.00001), plasma glycerol (P < 0.05) and free fatty acid (FFA) (P < 0.05) concentrations, and HGP (P < 0.05) were decreased in HFO + sitagliptin group compared with HFO group, but there was no significant difference between G and G + sitagliptin groups (P > 0.05). Gluconeogenesis in HFO group was five times of that in G rats (P < 0.01), but was significantly declined in HFO + sitagliptin group (P < 0.0001).

CONCLUSIONSGluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability, which was a result of reduced glycerol release from adipose tissues. The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity, thereby delaying or preventing the development of diabetes.

Animals ; Dipeptidyl-Peptidase IV Inhibitors ; therapeutic use ; Glucose ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Obesity ; drug therapy ; metabolism ; Pyrazines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sitagliptin Phosphate ; Triazoles ; therapeutic use