Synjardy (empagliflozin/metformin) / Boehringer Ingelheim, Eli Lilly - LARVOL DELTA

CER-4-T2D: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study (clinicaltrials.gov) - P=N/A | N=781430 | Active, not recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jul 2024 ➔ Jan 2026

HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Efficacy and safety of metformin versus empagliflozin on chronic kidney disease progression (MET-EMPA-CKD): a randomized controlled trial. (PubMed, Diabetol Metab Syndr) - P2/3 | "12-month metformin therapy demonstrated renoprotective effects comparable to empagliflozin, with a greater effect observed among non-diabetics as an exploratory insight. Metformin's renal actions were linked to antifibrotic and favorable autophagy effects while, empagliflozin preserved mainly tubular injury. Safety issues were generally comparable."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease • BECN1 • KIM1 • TGFB1

Preconditioning strategies for stem cells and exosomes: Transformative potential in diabetic wound treatment: A review. (PubMed, Int J Biol Macromol) - "Recent advances and future directions in the optimization of these strategies are discussed, emphasizing their potential to transform stem cell therapies for diabetic wounds. We highlight that specific preconditioning methods-such as hypoxia and pharmacological agents like metformin or empagliflozin-can selectively enhance exosomal miRNA cargo (e.g., miR-126, miR-139-3p) and downstream angiogenic signaling.Our synthesis underscores the superior translational potential of ADSC-derived exosomes over cell therapies, especially when optimized via preconditioning tailored to the diabetic microenvironment."

Journal • Review • Pain • MIR126 • MIR139

Bioequivalence Study to Compare Empagliflozin / Metformin 25 mg/ 1000 mg Extended-Release Tablet Versus Synjardy XR Tablets 25mg/1000mg (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Humanis Saglık Anonim Sirketi

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The Efficacy and Safety of Empagliflozin - Linagliptin and Empagliflozin- Metformin Therapy in Reduction of Body Weight in Type 2 Diabetic Patients . (clinicaltrials.gov) - P4 | N=200 | Completed | Sponsor: Bahria University

New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

LIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes (clinicaltrials.gov) - P=N/A | N=396 | Active, not recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Trial completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • Plasma NfL

Glimepiride, Empagliflozin, and Sitagliptin With Metformin for Type 2 Diabetes (clinicaltrials.gov) - P4 | N=172 | Completed | Sponsor: Bahria University | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

CT-L03-301: Efficacy and Safety of Pioglitazone Combination Therapy in Type 2 Diabetes Patients on a Background of Empagliflozin With Metformin (clinicaltrials.gov) - P3 | N=582 | Active, not recruiting | Sponsor: Celltrion | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison chart: Sodium-glucose cotransporter 2 (SGLT2) inhibitors. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparative effects of empagliflozin and metformin on metabolic dysfunction in polycystic ovary syndrome, a double blinded randomized control feasibility trial. (PubMed, BMC Womens Health) - P2/3 | "This study suggested that empagliflozin may offer greater metabolic benefits than metformin in overweight women with PCOS and prediabetes, although the adjusted results were not significantly different. These findings support the potential of SGLT2 inhibitors as alternative or add-on therapies."

Clinical • Journal • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome

Noninsulin drugs for type 2 diabetes. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Lobeglitazone improves glycaemic control as add-on therapy to empagliflozin plus metformin in patients with type 2 diabetes mellitus: A double-blind, randomised, placebo-controlled trial. (PubMed, Diabetes Obes Metab) - "Lobeglitazone as an add-on to empagliflozin and metformin significantly improved glycaemic control in patients with T2DM inadequately controlled on metformin and empagliflozin dual therapy. The treatment was well tolerated, with a low incidence of adverse events."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Copper Intrauterine Device-Associated ANCA Vasculitis: Rare Entity or a Coincidence? (KIDNEY WEEK 2025) - "Case Description A 50-year-old-female with a past medical history of hyperlipidemia, asthma, migraine, mild obesity, and pre- diabetes on metformin and empagliflozin presented to the clinic for evaluation of albuminuria of 139 mg/gm of creatinine (90 ml/min/1.73m2)...She was prescribed topical tacrolimus and clindamycin, along with oral doxycycline...Cutaneous small vessel vasculitis has been documented in association with chronic hepatitis A or C, oral contraception, hydralazine, propylthiouracil, allopurinol, β-lactams, streptokinase, tamoxifen, influenza vaccines, and environmental risk factors (silica exposure, farming, and chronic colonization with Staphylococcus aureus). One other case report has proposed a possible link between a copper-IUD and ANCA-associated retinal vasculitis, which was resolved following IUD removal. One caveat is the lack of a kidney or skin biopsy, as our patient declined."

ANCA Vasculitis • Asthma • CNS Disorders • Dermatitis • Dermatology • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Hidradenitis Suppurativa • Immunology • Infectious Disease • Inflammation • Influenza • Long-acting Reversible Contraceptives • Metabolic Disorders • Migraine • Obesity • Ocular Inflammation • Psoriasis • Renal Disease • Respiratory Diseases • Vasculitis

Overlapping Dilemma Involving the New Great Imposter (KIDNEY WEEK 2025) - "Case Description A 48-year-old woman with history of well controlled type 2 DM of 10-year duration on metformin and empagliflozin, presumed Stickler syndrome, hypertension on losartan and amlodipine, arthritis referred to nephrology for worsening albuminuria. Prompt diagnosis is important as family genetic testing and timely ERT can improve the overall outcome in FD. Albuminuria and proteinuria trend FD - Fabry disease"

Cardiovascular • Chronic Kidney Disease • Constipation • Diabetes • Diabetic Nephropathy • Fabry Disease • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Heart Failure • Hypertension • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Otorhinolaryngology • Rare Diseases • Renal Disease • Rheumatology

Analysis of the efficacy and safety of Hengliflozin combined with metformin in the treatment of diabetes mellitus complicated with hyperuricemia (ChiCTR) - P4 | N=70 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Guilin Medical University; The First Affiliated Hospital of Guilin Medical University

New P4 trial • Diabetes • Metabolic Disorders

The beneficial effects of empagliflozin-metformin combination on cardiovascular risk factors in type 2 diabetes mellitus patients. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Empagliflozin-Metformin combination therapy may offer additional benefits over metformin monotherapy in improving lipid parameters, IR, and oxidative stress in T2DM patients. These findings support the potential cardioprotective role of empagliflozin and highlight the need for long-term interventional studies to confirm our results."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus

Late Diagnosis of Prader-Willi Syndrome in an Adolescent With Significant Complications of Type 2 Diabetes. (PubMed, JCEM Case Rep) - "The patient was initially treated with multiple daily insulin injections prior to starting empagliflozin-metformin. The presence of developmental delays, short stature, and hypogonadism prompted genetic testing, which confirmed a diagnosis of Prader-Willi syndrome, a neurodevelopmental disorder associated with hyperphagia and early-onset obesity. This case underscored the severity of YO-T2D, risks of delayed healthcare access, and considerations for optimal diabetes management."

Journal • Acute Kidney Injury • CNS Disorders • Developmental Disorders • Diabetes • Diabetic Nephropathy • Diabetic Retinopathy • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Prader–Willi syndrome • Psychiatry • Renal Disease • Retinal Disorders • Type 2 Diabetes Mellitus

The Combination Empagliflozin/Metformin Attenuates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Diet-Induced Experimental Rat Model. (PubMed, Int J Mol Sci) - "Notably, co-therapy shows greater beneficial effects than single treatments. This protective effect appears to involve modulation of key transcription factors regulating lipid and carbohydrate metabolism, as well as influencing endogenous antioxidant defenses."

Journal • Preclinical • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Impact of empagliflozin as add-on to metformin vs metformin continuation on MASLD progression in type 2 diabetes: The IMAGIN Study. (PubMed, Nutr Metab Cardiovasc Dis) - "Empagliflozin + metformin improved liver parameters more effectively than metformin alone in T2D patients with MASLD. Baseline miR-122 and miR-21 may serve as potential biomarkers for steatosis and fibrosis improvement, respectively."

Journal • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • MIR122 • MIR21

Expression of GLUT-1 and SGLT-2 in the Chorioretina of Streptozotocin-induced Diabetic Rats After Administration of Empagliflozin. (PubMed, J Ophthalmic Vis Res) - "Both metformin and empagliflozin suppress the expression of SGLT-2 and GLUT-1 in the chorioretina of diabetic rats. In comparison, empagliflozin seems to be more potent in reducing this expression."

Journal • Preclinical • SLC2A1

Effects of 5:2 intermittent fasting meal replacement on body composition and abdominal fat distribution in adults with early type 2 diabetes (EASD 2025) - P=N/A | "The 5:2MR regimen may be more effective than metformin and empagliflozin in improving body composition and abdominal fat distribution in early T2DM, and is proposed as a therapeutic option."

Clinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Comparative assessment of treatment outcomes of empagliflozin add-on metformin and sitagliptin add-on metformin therapies in uncontrolled type 2 diabetes mellitus: findings from an observational study in Pakistan. (PubMed, J Health Popul Nutr) - "Empagliflozin as add on therapy in uncontrolled T2DM provided improvements in patients HbA1c, serum creatinine, and eGFR hence improving overall clinical outcomes and patient safety."

Clinical • Journal • Observational data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy. (PubMed, Biomedicines) - "A wide array of repurposed drugs-including antidiabetics (metformin, empagliflozin, gliclazide, semaglutide, and pioglitazone), antihypertensives (amlodipine, telmisartan, aliskiren, and rilmenidine), lipid-lowering agents (atorvastatin and alirocumab), anticonvulsants (topiramate and retigabine), antioxidant and neuroprotective agents (melatonin), and muscarinic receptor antagonists (pirenzepine, oxybutynin, and atropine)-have shown promising results in rodent models, reducing neuropathic pain behaviors and modulating underlying disease mechanisms. By bridging basic mechanistic insights with pharmacological interventions, this review aims to support translational progress toward mechanism-based therapies for DN."

Journal • Preclinical • Review • Diabetic Neuropathy • Inflammation • Neuralgia • Pain

Radiofrequency Ablation of Insulinoma with Significant Post-Procedural Hyperglycemia in Setting of Glucocorticoids (ENDO 2025) - "The patient was diagnosed with diabetes over 20 years ago and was previously on metformin and empagliflozin, which were recently discontinued due to hypoglycemic episodes... This case demonstrates the efficacy of EUS-RFA to treat insulinomas when surgery is contraindicated."

Acute Kidney Injury • Asthma • Chronic Obstructive Pulmonary Disease • Colon Cancer • Colorectal Cancer • Diabetes • Endocrine Cancer • Genetic Disorders • Hypoglycemia • Immunology • Metabolic Disorders • Nephrology • Neuroendocrine Tumor • Obesity • Oncology • Pancreatic Cancer • Renal Disease • Respiratory Diseases • Solid Tumor • Type 2 Diabetes Mellitus

Preserved C-peptide Five Years After LADA Diagnosis: Focus On Prandial Glycaemic Control (ENDO 2025) - "She was started on sc Novorapid 3-6 units 15 mins premeal at 1 unit to 10-gram carbs, and PO linagliptin 5 mg om. Empagliflozin and metformin were discontinued...However, the use of DPP4-inhibitors has been found useful. CONCLUSION RCTs utilizing C-peptide and CGM to inform the best regimens of insulin and/or OHA treatment for C-peptide preservation in LADA patients are needed."

Diabetes • Hypoglycemia • Immunology • Metabolic Disorders