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A closed-loop system (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. In this 16-week trial, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with a sensor-augmented insulin pump.

This open-label, 40-week, phase 3 trial assessed the efficacy and safety of tirzepatide, a weekly dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist under development for type 2 diabetes. Tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks.

We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications. This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA1c) of 7·5–10·5% (58–91 mmol/mol), body-mass index of 25 kg/m2 or greater, and established cardiovascular disease or a high risk of cardiovascular events. Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL. The primary endpoint was non-inferiority (0·3% non-inferiority boundary) of tirzepatide 10 mg or 15 mg, or both, versus glargine in HbA1c change from baseline to 52 weeks. All participants were treated for at least 52 weeks, with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events (MACE). Safety measures were assessed over the full study period. This study was registered with ClinicalTrials.gov, NCT03730662. Patients were recruited between Nov 20, 2018, and Dec 30, 2019. 3045 participants were screened, with 2002 participants randomly assigned to tirzepatide or glargine. 1995 received at least one dose of tirzepatide 5 mg (n=329, 17%), 10 mg (n=328, 16%), or 15 mg (n=338, 17%), or glargine (n=1000, 50%), and were included in the modified intention-to-treat population. At 52 weeks, mean HbA1c changes with tirzepatide were −2·43% (SD 0·05) with 10 mg and −2·58% (0·05) with 15 mg, versus −1·44% (0·03) with glargine. The estimated treatment difference versus glargine was −0·99% (multiplicity adjusted 97·5% CI −1·13 to −0·86) for tirzepatide 10 mg and −1·14% (−1·28 to −1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses. Nausea (12–23%), diarrhoea (13–22%), decreased appetite (9–11%), and vomiting (5–9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase. The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6–9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1–3% vs glargine 16%). Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51–1·08). 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study. In people with type 2 diabetes and elevated cardiovascular risk, tirzepatide, compared with glargine, demonstrated greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycaemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk. Eli Lilly and Company.

In this randomized, placebo-controlled trial, investigators evaluated the effects of the sodium–glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and a reduced ejection fraction with or without type 2 diabetes. The risk of worsening heart failure or cardiovascular death was lower among those who received dapagliflozin, regardless of the presence or absence of diabetes.

Short-chain fatty acids (SCFAs) are produced by various human gut microbes. SCFAs act as an energy source to the colonic epithelium and are also sensed by host signaling pathways that modulate appetite and inflammation. Deficiency of gut SCFAs is associated with type 2 diabetes. Zhao et al. found that adopting a high-fiber diet promoted the growth of SCFA-producing organisms in diabetic humans. The high-fiber diet induced changes in the entire gut microbe community and correlated with elevated levels of glucagon-like peptide-1, a decline in acetylated hemoglobin levels, and improved blood-glucose regulation. Science , this issue p. 1151 Increasing dietary fiber intake increases the abundance of short-chain fatty acid–producing gut microbes and relieves diabetes. The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

Adolescents with obesity and a poor response to lifestyle therapy alone were randomly assigned to receive either liraglutide or placebo subcutaneously once daily, in addition to lifestyle therapy. The use of liraglutide led to a significantly greater reduction in the standard-deviation score for the body-mass index than placebo.

Five-year data showed that among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing or resolving hyperglycemia, even among those with a BMI of less than 35. Observational studies 1 – 6 and randomized, controlled trials, which have generally been short-term studies, 7 – 19 have shown that bariatric surgery, when used specifically to treat diabetes, significantly improves glycemic control and reduces cardiovascular risk factors. In the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, we reported that, at 1 year and 3 years after randomization, both gastric bypass and sleeve gastrectomy were superior to intensive medical therapy alone in achieving excellent glycemic control (i.e., glycated hemoglobin ≤6.0%), reducing cardiovascular risk, improving quality of life, and decreasing medication use. 8 – 10 The current article provides results of the final, 5-year . . .

Safety data exist for subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, but not for the oral form. Here, oral semaglutide was assessed in a randomized, double-blind, placebo-controlled trial involving patients with type 2 diabetes at high cardiovascular risk; oral semaglutide was noninferior for cardiovascular safety.

In a multicenter, randomized, crossover trial involving children 1 to 7 years of age with type 1 diabetes, a closed-loop system was compared with sensor-augmented pump therapy in random order. The closed-loop system improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in a hypoglycemic state.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D ( n  = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was −1.07% (−1.19%, −0.95%) in the dorzagliatin group and −0.50% (−0.68%, −0.32%) in the placebo group (estimated treatment difference, −0.57%; 95% confidence interval: −0.79%, −0.36%; P  < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile. The SEED study is a phase 3 clinical trial demonstrating a beneficial effect on glycemic control of dorzagliatin, a glucokinase activator, in drug-naive patients with newly diagnosed type 2 diabetes.