insulin glargine (Galactus / Glaricon / Basalog)

Efficacy and Safety of Insulin Efsitora Versus Degludec in Adults with Type 2 Diabetes Who Are Insulin-Naïve: Japan Subgroup Analysis of QWINT-2.

Kiyosue Arihiro A, Inoue Mariko M, Takita Yasushi Y, Nasu Risa R et al.

The phase 3 QWINT-2 study demonstrated that once-weekly insulin efsitora alfa (efsitora) was noninferior to once-daily insulin degludec (degludec) in reducing glycated hemoglobin (HbA1c) at week 52 when added to existing noninsulin glucose-lowering agents in adults with type 2 diabetes who were insulin-naïve. A Japan subgroup analysis of QWINT-2 using two dosing algorithms is presented here. Participants from Japan were randomized 1:1 to efsitora or degludec and followed one of two dosing algorithms: a general dosing algorithm or an optional alternative dosing algorithm available for participants anticipated to require less insulin, characterized by a body weight ≤ 60 kg or HbA1c level ≤ 7.5% at baseline. Assessments included changes in HbA1c and fasting blood glucose from weeks 0-52, time spent in target glucose range (TIR) from weeks 48-52, and hypoglycemia from weeks 0-52. In total, 144 participants from Japan were included (efsitora, n = 71; degludec, n = 73). Demographic and baseline characteristics were generally balanced between treatment groups. From weeks 0-52, mean HbA1c decreased from 8.04% to 6.63% with efsitora and from 8.00% to 6.64% with degludec (estimated treatment difference, -0.01%). TIR was similar between efsitora and degludec from weeks 48-52. Rates of combined level 2 or 3 hypoglycemia were low overall (weeks 0-52) and during the initial dosing period (weeks 0-12). Level 3 hypoglycemia was not reported in any participants with efsitora and two participants with degludec. The incidence of adverse events was similar between efsitora and degludec. The efficacy and safety of efsitora were comparable with degludec using the general and alternative dosing algorithms in Japanese participants. Once-weekly efsitora was comparable to once-daily degludec in reducing HbA1c in Japanese participants who were insulin-naïve. The efficacy and safety of efsitora in Japanese participants were consistent with the overall QWINT-2 study population. NCT05362058.

Beyond glycemic control: differential effects of empagliflozin and sitagliptin on insulin sensitivity and a shared increase in adropin in type 2 diabetes.

Taha Otbah Salim OS, Azami Golnaz G, Saed Lotfollah L, Hakhamaneshi Mohammad Saeed MS et al.

Type 2 diabetes mellitus (T2DM) is characterized by metabolic and inflammatory disturbances beyond hyperglycemia. Hepatokines such as adropin have emerged as regulators of insulin resistance and vascular function, yet the comparative metabolic effects of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors on adropin remain unclear. This study compared the effects of empagliflozin versus sitagliptin, each added to metformin, on serum adropin, insulin resistance, glycemic control, lipid profile, and inflammation in adults with T2DM. In this single-center, randomized, open-label, parallel-group superiority trial with blinded outcome assessment and blinded statistical analysis, 100 adults with inadequately controlled type 2 diabetes mellitus (HbA1c ≥ 7.5%) receiving stable metformin therapy were allocated in a 1:1 ratio to receive empagliflozin 10 mg once daily or sitagliptin 100 mg once daily for a 12-week intervention period. The co-primary outcomes were changes in circulating adropin concentrations and insulin resistance, assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included changes in HbA1c, fasting insulin, lipid parameters, body weight, and tumor necrosis factor-α (TNF-α). All analyses were conducted according to the intention-to-treat principle. Ninety‑four participants completed the intervention; all were included in analyses. Serum adropin increased from 291 ± 133 to 362 ± 124 pg/mL with empagliflozin and from 299 ± 98 to 358 ± 126 pg/mL with sitagliptin (time effect: F = 19.67, p < .001). HOMA‑IR declined from 10.08 ± 4.44 to 6.65 ± 2.50 with empagliflozin and from 9.28 ± 2.97 to 7.15 ± 1.80 with sitagliptin (interaction: F = 4.85, p = .032, partial η² = 0.09). HbA1c decreased from 8.10 ± 0.53 to 7.04 ± 1.18 with empagliflozin and from 8.29 ± 0.66 to 7.62 ± 0.68 with sitagliptin (interaction: F = 4.30, p = .043, η² = 0.081). TNF‑α fell from 44.12 ± 21.52 to 30.78 ± 15.93 in empagliflozin and from 43.93 ± 21.33 to 37.65 ± 17.96 in sitagliptin (time effect: F = 37.09, p < .001). Empagliflozin produced greater reductions in fasting insulin (- 3.43 ± 2.34 µIU/mL vs. - 2.13 ± 1.17 µIU/mL, interaction p = .036), triglycerides (- 42.5 ± 23.9 mg/dL vs. - 21.9 ± 14.5 mg/dL, interaction p = .005), and a larger HDL‑C increase (+ 5.8 ± 3.1 mg/dL vs. + 3.3 ± 2.5 mg/dL, interaction p = .017). Body weight and BMI decreased similarly in both groups (time effect p < .001, no interaction). No serious adverse events occurred. Both empagliflozin and sitagliptin improved metabolic and inflammatory markers and were associated with comparable increases in circulating adropin. Empagliflozin conferred broader metabolic benefits, particularly in insulin resistance, glycemic control, and lipid profile. The parallel rise in adropin across treatment groups highlights its potential role as a treatment-responsive biomarker rather than a drug-specific effect. This trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT ID: IRCT20160625028627N8) on May 27, 2025 (Trial ID: 83720). The complete trial record is accessible at https://irct.behdasht.gov.ir/user/trial/83720/view.

A randomised clinical trial testing the safety of and metabolic responses to short-term duodenal infusion of recombinant RORDEP1 in healthy men.

Gæde Joachim J, Fan Yong Y, Lyu Liwei L, Gasbjerg Lærke Smidt LS et al.

RUMTOR-derived peptides (RORDEPs) 1 and 2 are polypeptides synthesised by specific strains of the human gut commensal Ruminococcus torques. Preclinical studies have shown that RORDEPs lower blood glucose via an impact on plasma incretins and an improvement of hepatic insulin sensitivity. In a randomised, placebo-controlled, crossover trial, we here explore the safety and tolerability of, as well as any metabolic responses to, a duodenal infusion of recombinant RORDEP1 (r-RORDEP1) given to healthy men after oral intake of a liquid mixed meal. Seventeen healthy, normal-weight men between 18 and 35 years of age were randomised through block randomisation to receive either r-RORDEP1 or placebo as the initial intervention at Gentofte Hospital, Denmark. Exclusion criteria were use of any form of medication, use of antibiotics during the 3 months before intervention, lactose intolerance, smoking, alcohol or drug abuse, or the use of probiotics or creatine as dietary supplements during the study period. Blocks were created prior to trial initiation. Both participants and investigators were blinded to treatment. Following intake of a standardised liquid meal, r-RORDEP1 was given via a naso-duodenal tube as an initial bolus of 0.0108 mg/kg body weight followed by a continuous infusion of 0.25 µg kg-1 min-1 for 170 min. Primary outcomes were changes in plasma concentrations of incretins and peptide YY, while secondary endpoints were safety and tolerability, and changes in plasma insulin, C-peptide and glucose. All 17 participants completed the trial. Duodenal infusion of r-RORDEP1 was well tolerated and without changes in biochemical measures of haematological, liver or renal functions. Compared with placebo, the bolus of r-RORDEP1 induced an early (at 15 or 30 min) rise in plasma glucagon-like peptide-1, insulin and C-peptide (q=0.001, q=0.001 and q=0.003, respectively) and a decline in plasma gastric inhibitory polypeptide and glucose (q=0.02 and q=0.006, respectively), while also increasing whole-body insulin sensitivity as measured with the Matsuda index of insulin sensitivity (p=0.049). Short-term duodenal infusion of r-RORDEP1 is safe and well tolerated and elicits changes in plasma incretins, insulin and glucose, and a measure of whole-body insulin sensitivity, aligning with findings in rodents, supporting the hypothesis that RORDEPs hold a role in impacting host metabolism. ClinicalTrials.gov NCT06923839 FUNDING: EFSD/Lilly European Diabetes Research Programme 2021, RUCILP F-19235-01-64 - NNF21SA0070428 grant and NNF23SA0084103 grant, the latter two from the Novo Nordisk Foundation.

Management of Pregnancy in Type 1 Diabetes Using a Novel Automated Insulin Delivery System.

Bhasin Kanchan K, Bowdler Marissa M, Scifres Christina M CM, Cleary Erin M EM et al.