Search

Aim: Use of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) for glycaemic control is increasing in individuals with type 2 diabetes (T2D) for their additional benefits on heart failure and chronic kidney disease. However, SGLT2is generally reduce body weight, which might promote sarcopenia in older individuals. We evaluated the effects of the SGLT2i empagliflozin on muscle mass and strength in addition to glucose control in elderly adults with T2D. Materials and Methods: Individuals with T2D aged ≥65 years with body mass index ≥22 kg/m2 and glycated haemoglobin (HbA1c) 7.0%‐10.0% were randomized 1:1 to once‐daily empagliflozin 10 mg or placebo for 52 weeks. The primary endpoint was change from baseline in HbA1c at week 52. Secondary endpoints included changes from baseline in muscle mass and strength. Results: Of the 129 individuals randomized, 72.4% were men, mean age 74.1 years, body mass index 25.6 kg/m2 and HbA1c 7.6%. The placebo‐adjusted mean change from baseline in HbA1c at week 52 with empagliflozin was −0.57% [95% confidence interval (CI) −0.78, −0.36]. Change in body weight was −3.26 kg and −0.90 kg with empagliflozin and placebo, respectively (placebo‐adjusted difference: −2.37 kg; 95% CI −3.07, −1.68). Placebo‐adjusted change in muscle mass was −0.61 kg (95% CI −1.61, 0.39), fat mass −1.84 kg (95% CI −2.65, −1.04) and grip strength −0.3 kg (95% CI −1.1, 0.5). Conclusions: Empagliflozin improved glucose control and reduced body weight without compromising muscle mass or strength in elderly adults with T2D in this trial. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control. Materials and Methods: This was a randomized, double‐blind, placebo‐controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24. Results: Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference −0.99 and −0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P <.0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2‐hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P =.2422 and.7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee‐confirmed diabetic ketoacidosis events were reported. Conclusions: In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia. [ABSTRACT FROM AUTHOR]

This 24‐week, double‐blind, placebo‐controlled, phase III trial evaluated the efficacy and safety of linagliptin in 206 Chinese patients with inadequately controlled (glycated haemoglobin [HbA1c] 7.5%–10.0%) type 2 diabetes mellitus (T2DM) receiving insulin (basal or premixed) ± metformin. Patients were randomized (1:1) to receive linagliptin 5 mg/d or placebo. The decrease from baseline in HbA1c (primary endpoint) was greater with linagliptin than with placebo (−0.61% vs. −0.20%, adjusted mean difference −0.40%; P = 0.0016). Linagliptin demonstrated significantly greater improvement in 2‐hour postprandial glucose (−1.77 mmol/L [−31.95 mg/dL]; P < 0.001), and a numerical reduction in fasting plasma glucose (−0.34 mmol/L [−6.2 mg/dL]; P = 0.2241) versus placebo. Proportionally more patients on linagliptin achieved a HbA1c reduction of ≥0.5% versus those on placebo (odds ratio 2.293, P < 0.01). Adverse events in both groups were similar, with no new safety findings or clinically relevant changes in body weight. Among investigator‐defined hypoglycaemic events (linagliptin: 17.3%; placebo: 12.7%; odds ratio 1.48, P = 0.337), none were severe. In Chinese patients with T2DM, linagliptin add‐on to insulin improved glycaemic control and was well tolerated, without increased risk of hypoglycaemia or weight gain. [ABSTRACT FROM AUTHOR]

Aims The MARLINA- T2D study (, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/mol), estimated glomerular filtration rate ( eGFR) ≥30 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio ( UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin ( n = 182) or placebo ( n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results Baseline mean HbA1c and geometric mean ( gMean) UACR were 7.8% ± 0.9% (62.2 ± 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was −0.60% (−6.6 mmol/mol) (95% confidence interval [ CI], −0.78 to −0.43 [−8.5 to −4.7 mmol/mol]; P < .0001). The placebo-adjusted gMean for time-weighted average of percentage change in UACR from baseline was −6.0% (95% CI, −15.0 to 3.0; P = .1954). The adverse-event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. Conclusions In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics. [ABSTRACT FROM AUTHOR]

This study investigated the long-term efficacy and safety of empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes mellitus (T2DM). Of 666 patients treated with empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily for 24 weeks, 472 patients (70.9%) were treated in a double-blind extension trial for ≥52 weeks. Pre-specified exploratory endpoints included changes from baseline in HbA(1c), weight and blood pressure at week 76. At week 76, adjusted mean differences versus placebo in change from baseline in HbA(1c) were -0.7% (-8 mmol/mol) with empagliflozin 10 mg or 25 mg (both p<0.001), in weight were -1.8 kg and -1.6 kg with empagliflozin 10 mg and 25 mg, respectively (both p<0.001), and in systolic blood pressure (SBP) were -2.2 mmHg with empagliflozin 10 mg (p=0.021) and -2.1 mmHg with empagliflozin 25 mg (p=0.029). Sensitivity analyses provided consistent results for HbA1c and weight, but showed no significant difference between empagliflozin and placebo in change from baseline in SBP. Adverse events (AEs) were reported in 81.7%, 82.0% and 81.3% of patients on empagliflozin 10 mg, 25 mg and placebo, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in 23.7%, 19.4% and 15.6% of patients on empagliflozin 10 mg, 25 mg and placebo, respectively; one patient each on empagliflozin 10mg and placebo required assistance. In conclusion, empagliflozin as add-on to metformin plus sulphonylurea for 76 weeks was well tolerated and led to sustained reductions in HbA1c and weight versus placebo. CLINICALTRIALS.GOV: NCT01289990. [ABSTRACT FROM AUTHOR]