metformin + sitagliptin (Januvia ER / Janumet ER / Janumet XR)

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

Chakraborty Radhika R, Mohapatra Debadatta D, Biswas Tathagata T, Ramasubbu Mathan Kumar MK et al.

Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50 mg/day) or metformin (1000 mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL∶HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD = 0.61 (0.02 to 1.21), p = 0.04; metformin: MD = 0.45 (0.07 to 0.83), p = 0.02], with no significant between-group difference in unadjusted analysis (p = 0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (β = -0.324, p = 0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (β = -1.209, p = 0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Correction: Obesity-induced extracellular vesicles proteins drive the endometrial cancer pathogenesis: therapeutic potential of HO-3867 and Metformin.

Sakaue Takahiko T, Dorayappan Kalpana Deepa Priya KDP, Zingarelli Roman R, Khadraoui Wafa W et al.

Correction: Comparative analysis of glucagon-like peptide-1 receptor agonists, metformin, and inositol in improving anthropometric and metabolic outcomes in women with polycystic ovary syndrome: a network meta-analysis.

Omarion Asad A, Ayasa Yaman Y, Omarion Zainab Z, Jayouse Batoul B et al.

[This corrects the article DOI: 10.3389/fendo.2026.1833904.].

Overweight and obesity induce Toll-like receptor 2-induced Type I IFN signaling.

Elkins Megan M, Al-Musa Amer A, Chiñas Marcos M, Woods Brian B et al.

Toll-like receptor 2 (TLR2) is an innate immune receptor linked to obesity primarily via NF-κB activation. Using a mouse model of overnutrition and in vitro TLR2 stimulation of human peripheral blood mononuclear cells, we show that lipids, advanced glycation end products, and low-density lipoproteins extend TLR2 signaling beyond NF-κB to promote Type I IFN production and signaling, establishing the relevance of this pathway to human obesity. This response was abolished by pharmacologic inhibition of the receptor for advanced glycation end products, which recognizes glycated proteins and lipids. In vivo dietary reversal, metformin, and tirzepatide each reduced diet-induced inflammation, but differed in their metabolic effects: dietary reversal reduced weight gain and LDL, tirzepatide reduced weight without lowering LDL, and metformin exerted anti-inflammatory effects independent of weight or LDL. These findings identify TLR2-Type I IFN signaling as a feature of diet-induced inflammation and highlight the diverse immunomodulatory effects of weight-management therapies.