<h4>Background</h4>Triple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor).<h4>Methods</h4>Following preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models.<h4>Results</h4>Eight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03).<h4>Conclusion</h4>Triple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.

<h4>Background</h4>Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by obesity, insulin resistance, and cardiometabolic risks. Lifestyle intervention is first-line therapy, but drug therapy is often necessary. Common treatments include metformin, myoinositol, and glucagon-like peptide-1 (GLP-1) receptor agonists. The comparative metabolic efficacy of these treatments remains unclear.<h4>Methods</h4>We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) according to PRISMA-NMA guidelines. Eligible studies recruited non-menopausal women with PCOS and evaluated GLP-1 receptor agonists, metformin, or myoinositol (± folic acid [FA]) alone or in combination versus placebo or active comparators. The primary outcome was body weight change, while secondary outcomes included body mass index (BMI), waist circumference, and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Outcomes were synthesized using a frequentist random-effects NMA, and the CINeMA framework was used to assess certainty.<h4>Results</h4>Sixteen RCTs were included. GLP-1 + metformin was the most effective intervention for weight reduction (MD -5.58 kg; 95% CI -8.57 to -2.59) and BMI decrease (MD -2.17; 95% CI -2.77 to -1.58). GLP-1 monotherapy also showed decreases in weight (MD -5.22 kg) and BMI (MD -2.00). Waist circumference was significantly reduced by GLP-1 alone (MD -4.70 cm). None ofthe interventions showed significant effects on HOMA-IR, and results were marked by heterogeneity. Sensitivity analyses confirmed robustness for weight and BMI outcomes.<h4>Conclusions</h4>GLP-1 receptor agonists combined with metformin appear to be the most effective pharmacologic therapies for anthropometric improvement, specifically body weight and BMI reduction, in women with PCOS. These conclusions are limited to anthropometric and metabolic parameters, reproductive, endocrine, and patient-centered outcomes were not evaluated in this analysis and therefore no claims of overall superiority in PCOS management can be made. Further long-term and head-to-head RCTs including a broader range of outcomes are needed.<h4>Systematic review registration</h4>https://osf.io/zyhws/, identifier 10.17605/OSF.IO/ZYHWS.

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) often requires combination therapy when metformin alone becomes insufficient. Empagliflozin (SGLT2 inhibitor) and sitagliptin (DPP-4 inhibitor) are commonly used add-on agents with differing metabolic profiles. This systematic review and meta-analysis compared their glycaemic, cardiometabolic and safety outcomes when added to metformin.<h4>Methods</h4>Following PRISMA guidelines, PubMed, Embase, Cochrane, Scopus and ClinicalTrials.gov were searched from inception to September 2025. Randomized trials and observational studies comparing empagliflozin + metformin versus sitagliptin + metformin in adults with T2DM were included. Primary outcomes were changes in HbA1c, body weight, fasting glucose, lipid profile and blood pressure. Safety outcomes included urinary tract infections, genital infections, gastrointestinal disturbances and rash. Risk of bias was assessed using RoB 2.0 and the Newcastle-Ottawa Scale. Random-effects models were used for meta-analyses, and meta-regression explored the impact of empagliflozin dose.<h4>Results</h4>Eleven studies met eligibility criteria. Empagliflozin produced greater reductions in HbA1c, body weight, fasting glucose and systolic blood pressure compared with sitagliptin. Lipid changes were modest and inconsistent. Rates of urinary infections, gastrointestinal symptoms and rash were comparable between groups, whereas genital infections were significantly higher with empagliflozin. Rare but serious adverse events associated with SGLT2 inhibitors, including Fournier's gangrene and lower limb amputations, were not reported in the included trials. Meta-regression showed no meaningful dose-response relationship for glycaemic or weight outcomes.<h4>Conclusions</h4>In patients with T2DM on metformin, empagliflozin offers superior glycaemic and cardiometabolic benefits compared with sitagliptin, with an increase in genital infections. Both therapies are well tolerated, supporting empagliflozin as an effective metabolic add-on option.<h4>Trial registration</h4>PROSPERO ID: CRD420251152360.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major causes of cognitive decline. Antidiabetic medications such as metformin, pioglitazone, and GLP-1 receptor agonists have been proposed as potential neuroprotective therapies. We assessed whether these agents slow cognitive decline or disease progression in people with AD or MCI. PubMed, Embase, and Cochrane Central were searched for randomized controlled trials and observational studies of metformin, pioglitazone, or GLP-1 receptor agonists in AD/MCI. Results were synthesized narratively by drug class. Eleven studies met the inclusion criteria. Metformin, particularly in early-stage disease and metabolically vulnerable groups, demonstrated improvements in episodic memory and selective executive outcomes. Observational data in diabetic MCI suggested improved cognition and preservation of hippocampal and cortical structure, with limited amyloid-β and tau changes. Pioglitazone findings varied. Benefits were mainly reported in mild AD with type-2 diabetes, but not in non-diabetic AD/MCI. GLP-1 receptor agonists demonstrated preserved cerebral glucose metabolism and improved blood-to-brain glucose transport but did not improve cognitive function. Current evidence does not support antidiabetic therapies as effective treatments in AD/MCI. Any benefits appear to depend on disease stage and metabolic status, with metformin being the most promising candidate. Larger, longer-duration biomarker-defined trials are needed to determine whether any sustained clinical benefit is observed.

Diabetes is a non-communicable disease which is attaining increasing importance among the adult population in both developed and developing countries. Pre-diabetes is a precursor condition for type 2 Diabetes mellitus. Although in many cases it is reversible, Pre-diabetes frequently remains undiagnosed and therefore risk of developing type 2 Diabetes Mellitus is increased. Lifestyle modification is more effective mode of preventing diabetes and reduction of 40%-70% with pre-diabetes. While there is increasing evidence to prove the efficacy of pharmacotherapy in prevention of diabetes in adults with pre-diabetes, pharmaceutical treatment options other than metformin are associated with adverse effects that limit their use for pre-diabetes. It is considered to be an at risk state, with high chances of developing diabetes. While, pre-diabetes is commonly an asymptomatic condition, there is always presence of pre-diabetes before the onset of diabetes. This aim of this study is to describe the challenges associated with diagnosis of pre-diabetes, the possible adverse medical outcomes associated with pre-diabetes and the treatment options and rationale for their use in context of pre-diabetes. This research topic is selected for prevention of type 2 Diabetes Mellitus by identification of high risk subjects and early dietary intervention in the form of Haridra. Therefore, an attempt has been made to study the clinical efficacy of Haridra In Prameha Purvaroop W.S.R. To Prediabetes.

Biochemical screen correction possibilities in patients with non-alcoholic fatty liver disease with diabetes mellitus The rationale for this study is the controversial data regarding the efficacy of hepatoprotectors and antioxidants for lipid profile correction in non-alcoholic fatty liver disease, the prevalence of which is increasing especially in association with diabetes mellitus. We examined 100 non-alcoholic fatty liver disease patients (40–75 years old) with concomitant type 2 diabetes mellitus (n = 73) or without it (n = 27), the groups were standardized by age and gender. In patients with non-alcoholic fatty liver disease with diabetes mellitus we revealed significantly higher rates of total cholesterol, triglycerides and atherogenic factor in association with a significantly lower high-density lipoproteins level versus the group of patients without concomitant diabetes. We recommended the modification of lifestyle as basic management of their condition to all patients, hypoglycemic therapy with metformin to persons with concomitant diabetes mellitus and rosuvastatin to patients with non-alcoholic fatty liver disease without diabetes.

Biguanides and sulfonylureas as combination therapy in NIDDM. Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy. Published in Diabetes care (1990)