Search

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method., Materials and Methods: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets., Results: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia., Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China., Materials and Methods: This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint)., Results: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group., Conclusions: Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To demonstrate the noninferiority of alogliptin to acarbose, in terms of antidiabetic efficacy, in Chinese people with uncontrolled type 2 diabetes (T2D) and high cardiovascular risk., Materials and Methods: ACADEMIC (NCT03794336) was a randomized, open-label, phase IV study conducted at 46 sites in China. Antidiabetic treatment-naive or metformin-treated adults with uncontrolled T2D (glycated haemoglobin [HbA1c] 58.0-97.0 mmol/mol) were randomized 2:1 to alogliptin 25 mg once daily or acarbose 100 mg three times daily for 16 weeks. All participants had a documented history of coronary heart disease or high cardiovascular risk at screening and received aspirin (acetylsalicylic acid) 100 mg daily throughout the trial. The primary endpoints were change in HbA1c versus baseline, and the incidence of gastrointestinal adverse events (AEs). Safety and tolerability were also assessed., Results: A total of 1088 participants were randomized. Alogliptin was noninferior to acarbose for the change in Week-16 HbA1c (least-squares mean change [standard error] -11.9 [0.4] vs. -11.4 [0.5] mmol/mol, respectively; difference between arms -0.5 [0.7] mmol/mol; 95% confidence interval -1.9 to 0.8 mmol/mol), and was associated with a lower incidence of gastrointestinal AEs (8.9% vs. 33.6%, respectively; P < 0.0001). More alogliptin than acarbose recipients achieved HbA1c <53.0 mmol/mol without gastrointestinal AEs (48.0% vs. 32.7%; P < 0.0001). Discontinuations due to treatment-related AEs were less frequent with alogliptin than acarbose (0.3% vs. 2.5%)., Conclusions: Glycaemic control was comparable between alogliptin and acarbose, but the gastrointestinal tolerability of alogliptin was better. More patients achieved target HbA1c without gastrointestinal AEs with alogliptin, suggesting that this agent may be preferred in clinical practice., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To determine the safety of a higher starting dose of basal insulin in overweight/obese patients with type 2 diabetes (T2D)., Materials and Methods: This 16-week, randomized, multicentre, open-label trial enrolled adults with T2D (body mass index 25-40 kg/m 2 ) and suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7.5-11.0% [58-97 mmol/mol] and fasting plasma glucose [FPG] >9.0 mmol/L) with two to three oral anti-hyperglycaemic drugs at 51 centres in China. Patients were randomized (1:1) to a higher (0.3 U/kg) or standard (0.2 U/kg) starting dose of insulin glargine 100 U/mL, which was then titrated to achieve a self-monitored fasting blood glucose (FBG) of 4.4 to 5.6 mmol/L. The primary endpoint was the percentage of patients with ≥1 episode of overall confirmed hypoglycaemia (≤3.9 mmol/L or severe)., Results: At the end of study (n = 866), 11.0% patients treated with the 0.3 U/kg starting insulin dose experienced overall confirmed hypoglycaemia versus 8.6% of patients treated with 0.2 U/kg (estimated difference 2.1%, 95% confidence interval - 1.68, 5.89). The proportions of patients with symptomatic (9.8% vs 7.0%; P = 0.128) and nocturnal hypoglycaemia (2.7% vs 1.2%; P = 0.102) were similar in the two groups. There were no events of severe hypoglycaemia or FBG <3.0 mmol/L during the 16-week treatment, and achievement of HbA1c <7.0% (53 mmol/mol) (37.1% vs 37.1%) or FPG <5.6 mmol/L (15.9% vs 16.3%), <6.1 mmol/L (27.6% vs 26.1%), or < 7.0 mmol/L (48.8% vs 48.3%) without hypoglycaemia were comparable in the two groups. Moreover, the mean time was shorter (4.53, 3.95 and 2.74 weeks vs 5.51, 5.21 and 3.64 weeks) and number of titrations was lower (3.5, 3.0 and 2.0 vs 4.3, 4.0 and 2.8) to achieve self-monitored FBG targets of <5.6, <6.1 and <7.0 mmol/L in the higher versus the standard insulin dose group (all P < 0.01)., Conclusions: Among overweight/obese patients with T2D, a higher insulin starting dose was as safe as the standard starting dose, and self-monitored FBG targets were achieved earlier with the higher versus the standard dose., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)