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

Longitudinal Changes in Corneal Epithelial and Central Corneal Thickness in Type 2 Diabetes Assessed by AS-OCT: A Real-World Study. (PubMed, Clin Ophthalmol) - "In this retrospective observational cohort study, 40 adults with type 2 diabetes receiving one of two routinely prescribed treatment regimens (vildagliptin-metformin, n=19; empagliflozin-metformin, n=21) underwent AS-OCT at baseline, 3 months, and 12 months. Corneal structural parameters showed no statistically detectable longitudinal change or between-group difference over 12 months. Given the modest sample size and observational design, these findings should be considered hypothesis-generating and require confirmation in larger prospective studies."

Journal • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Recognizing Euglycemic Diabetic Ketoacidosis in the Era of SGLT2 Inhibitors: A Case Report. (PubMed, Cureus) - "We present the case of a 51-year-old male with long-standing poorly controlled type 2 diabetes mellitus who developed euDKA shortly after initiation of empagliflozin/metformin therapy...The patient required intensive care management with intravenous fluids, insulin infusion, electrolyte monitoring, and dextrose-containing fluids, with subsequent complete resolution of metabolic abnormalities. This case adds to the growing body of literature describing euDKA in patients receiving SGLT2 inhibitor therapy in the setting of reduced oral intake and poorly controlled diabetes mellitus."

Journal • Critical care • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Gut microbiota from empagliflozin-treated patients ameliorates atherosclerosis in high-fat diet-fed ApoE-/- mice (EASD 2026) - "Materials and Fecal microbiota collected from patients with type 2 diabetes before and after 3 months of treatment with empagliflozin or metformin were transplanted into antibiotic-treated high-fat fed ApoE -/- mice. Empagliflozin may attenuate weight gain, reduce aortic inflammatory factor expression, decrease atherosclerotic plaque burden, and improve atherosclerotic lesions through modulation of the gut microbiota. The mechanism by which empagliflozin ameliorates atherosclerosis may be related to the gut microbiota-mediated bile acid-FXR-SMPD axis."

Gut Microbiota • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • APOE • ICAM1 • IL6

Efficacy and safety of anagliptin add-on therapy in patients with type 2 diabetes inadequately controlled by metformin and empagliflozin (EASD 2026) - P3 | "The addition of anagliptin to a metformin and empagliflozin regimen significantly improved glycemic control without increasing safety concerns or negatively impacting blood pressure and renal function. Triple therapy with anagliptin, metformin, and empagliflozin represents a potent and safe therapeutic option for patients with T2DM requiring further glucose lowering."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Neuroprotective effects of empagliflozin and metformin combined therapy on rotenone induced Parkinsonism in Wistar rats via PI3K and PPARγ modulation. (PubMed, Sci Rep) - "Additionally, the combined treatment restored PI3K/AKT signaling activity and significantly upregulated PPAR-γ expression (p < 0.001 vs. ROT). Collectively, these findings suggest that combined metformin and empagliflozin therapy exerts enhanced neuroprotective effects through modulation of protein aggregation pathways, highlighting a promising drug-repositioning strategy for Parkinsonism."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • PPARA • PPARG

Efficacy and safety of a triple fixed-dose combination of empagliflozin, evogliptin and metformin in patients with type 2 diabetes inadequately controlled: a Phase III randomised controlled trial (EASD 2026) - P3 | "The addition of empagliflozin to metformin and evogliptin significantly improved glycemic control and multiple metabolic parameters with a favorable safety profile. These results confirm the clinical efficacy and safety of a triple therapy approach, supporting the use of a single-tablet triple fixed-dose combination of metformin, evogliptin, and empagliflozin to simplify complex treatment regimens and improve outcomes in patients with T2DM."

Clinical • P3 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Bioequivalence Evaluation of Immediate-Release Empagliflozin/Metformin Fixed-Dose Combination Tablets Under Fed Conditions in Healthy Mexican Subjects and Exploratory Analysis of Metformin Dose Proportionality. (PubMed, Pharmaceuticals (Basel)) - P=N/A | "An exploratory power-model analysis indicated a modest trend toward less-than-dose-proportional metformin exposure across the 500-1000 mg range (slope β ≈ 0.77-0.78). NCT07633015, NCT07633054, NCT07633028, and NCT07633041."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Perioperative Euglycemic Diabetic Ketoacidosis in a Patient on SGLT2 Inhibitors: The Role of Hemorrhage, Interdisciplinary Communication, and Invasive Monitoring (ASA 2026) - "A 47-year-old female on empagliflozin/metformin underwent exploratory laparotomy with modified radical hysterectomy and bilateral salpingo-oophorectomy for uterine leiomyomata...An arterial line proactively placed by the anesthesia team enabled rapid ABG confirmation of pH 7.228, facilitating early interdisciplinary recognition, ICU transfer, and insulin infusion. This case illustrates hemorrhage as a novel 'second hit' precipitating SGLT2i-associated eDKA and supports the critical role of interdisciplinary communication in its early detection."

Clinical • Gynecology • Hematological Disorders • Metabolic Disorders • Solid Tumor • Uterine Leiomyoma

The Perfect Metabolic Storm: Synergy Between Prolonged Fasting and SGLT2i Therapy (ASA 2026) - "70-year-old male with type 2 diabetes managed on empagliflozin-metformin and dulaglutide presented for robotic hiatal hernia repair. Despite euglycemia (161 mg/dL), serum beta-hydroxybutyrate was critically elevated at 2.94 mmol/L. This case demonstrates that even guideline-directed cessation of SGLT2 inhibitors may fail to prevent intraoperative euglycemic ketoacidosis when combined with prolonged starvation stress."

Diabetes • Gastroenterology • Metabolic Disorders • Type 2 Diabetes Mellitus

EMPOWER: The Effect of Empagliflozin and Metformin on Oxidative Capacity and Microvascular Reactivity of Skeletal Muscle in Patients With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P4 | N=54 | Recruiting | Sponsor: University Medical Centre Ljubljana

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

Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis. (PubMed, Probl Endokrinol (Mosk)) - "Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/α-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-α upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a «muscle-glucose feedback loop» with hepatic gluconeogenesis amplification, yielding..."

Journal • Diabetes • Fatigue • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Sarcopenia • Targeted Protein Degradation • Type 2 Diabetes Mellitus • AMPK • GDF15 • IGF1 • IL15 • IL6 • SLC2A4 • TNFA

The Potential Roles of Oral Hypoglycemic Agents to Modulate Mitochondrial Function in Type 1 Diabetes Mellitus: A Scoping Review. (PubMed, Life (Basel)) - "Four preclinical studies suggested that metformin and empagliflozin may improve mitochondrial quality control in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner by enhancing biogenesis and preventing mitochondrial fission in T1DM. Certain OHAs may modulate mitochondrial dysfunction in T1DM, but clinical translation remains speculative and requires further investigation regarding their potential as adjunctive therapy."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • AMPK

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 | Completed | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • Plasma NfL

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 Sagl?k Anonim Sirketi

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

What Type of Diabetes Does This Patient Have? (ENDO 2026) - "His DMT2 was initially well-controlled with oral medications of empagliflozin and metformin, but within the past year his glycemic control had worsened despite escalation of oral medications and the addition of tirzepatide weekly injections...Conclusion This case highlights the growing spectrum of DM and emphasizes the importance of recognizing and treating patients who present with features not consistent with only type 1 or type 2 DM. Management remains difficult and must be individually developed for each patient."

Clinical • Benign Prostatic Hyperplasia • Cardiovascular • Diabetes • Dyslipidemia • Endocrine Disorders • Gout • Hypertension • Immunology • Inflammatory Arthritis • Metabolic Disorders • Type 2 Diabetes Mellitus

Euglycemic Diabetic Ketoacidosis after GLP-1 Receptor Agonist Initiation in A Patient Receiving Chronic SGLT2 Inhibitor Therapy (ENDO 2026) - "He had been treated with empagliflozin and metformin for approximately two years without prior episodes of ketoacidosis... This case demonstrates that initiation of GLP-1 receptor agonist may precipitate euglycemic diabetic ketoacidosis (euDKA ) in patients receiving chronic SGLT2 inhibitor therapy, particularly in the setting of poor baseline glycemic control. Although GLP-1 RAs are not independently associated with diabetic ketoacidosis, their effects on appetite suppression, reduced caloric intake, and relative insulin deficiency may potentiate SGLT2 inhibitor-mediated ketogenesis, thereby increasing euDKA risk. Clinicians should maintain heightened awareness of euDKA risk when initiating GLP-RAs in patients on SGLT2 inhibitors and emphasize symptom recognition and sick-day management."

Clinical • Diabetes • Endocrine Disorders • Metabolic Disorders • Pulmonary Disease • Type 2 Diabetes Mellitus

Acute Pancreatitis Revealing Familial Chylomicronemia Syndrome in a Complex Metabolic Setting (ENDO 2026) - "Medication review demonstrated inconsistent adherence to metformin, glipizide, empagliflozin/metformin XR, fenofibrate, and incretin-based therapy. While no causal relationship can be established, the coexistence of severe genetic dyslipidemia and incretin-based therapy illustrates the clinical complexity encountered in high-risk metabolic phenotypes and underscores the need for individualized therapeutic assessment and close monitoring. Early diagnosis of FCS and timely initiation of emerging RNA-targeted therapies, such as olezarsen, are critical to preventing recurrent pancreatitis and improving long-term outcomes."

Asthma • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertension • Hypertriglyceridemia • Immunology • Metabolic Disorders • Obesity • Pancreatitis • Respiratory Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • APOA5

Latent Autoimmune Diabetes in Adults Unmasked by SGLT2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis (ENDO 2026) - "His history was notable for progressively worsening glycemic control despite escalating oral therapy, including empagliflozin/metformin, glipizide, pioglitazone, and alogliptin, with a glycosylated hemoglobin (HbA1c) of 11.3%. The combination of young age, non-obesity, and treatment failure on multiple oral agents should prompt autoantibody and C-peptide testing. SGLT2 inhibitors are not approved for type 1 diabetes and should not be used in patients with insulin-deficient states or prior diabetic ketoacidosis."

Clinical • Diabetes • Genetic Disorders • Immunology • Infectious Disease • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Acute Pancreatitis Revealing Familial Chylomicronemia Syndrome in a Complex Metabolic Setting (ENDO 2026) - "Medication review demonstrated inconsistent adherence to metformin, glipizide, empagliflozin/metformin XR, fenofibrate, and incretin-based therapy. While no causal relationship can be established, the coexistence of severe genetic dyslipidemia and incretin-based therapy illustrates the clinical complexity encountered in high-risk metabolic phenotypes and underscores the need for individualized therapeutic assessment and close monitoring. Early diagnosis of FCS and timely initiation of emerging RNA-targeted therapies, such as olezarsen, are critical to preventing recurrent pancreatitis and improving long-term outcomes."

Asthma • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertension • Hypertriglyceridemia • Immunology • Metabolic Disorders • Obesity • Pancreatitis • Respiratory Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • APOA5

Comparison between the Efficacy of Empagliflozin Andmetformin Versus Sitagliptin and Metformin in Thetreatment of Non-Alcoholic Fatty Liver Disease (NAFLD)With Diabetes Mellitus (DM) (ENDO 2026) - "In this study, both treatment combinations demonstrated comparable efficacy in managing key metabolic and hepatic parameters in patients with NAFLD and DM. However, the combination of Empagliflozin and Metformin was superior in reducing ALT levels, suggesting a potentially greater benefit for liver inflammation in this patient population. Further studies with larger sample sizes are recommended to confirm these findings."

Clinical • Diabetes • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Retinal and optic nerve measures after initiation of empagliflozin plus metformin versus metformin alone in early type 2 diabetes: a prospective observational comparative study. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "In this exploratory prospective observational study, empagliflozin added to metformin was associated with short-term OCT and VEP changes compatible with a potential neuroprotective signal in early T2DM. Findings require confirmation in longer-term randomised or robust quasi-experimental studies."

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

ACL24-PC020: Clinical Study to Determine Bioequivalence Between Two Oral Medications of Empagliflozin/Metformin in 12.5 mg / 1000 mg Tablets Under Fed Conditions. (clinicaltrials.gov) - P=N/A | N=42 | Completed | Sponsor: ADIUM

New trial

ACL24-PC019: Clinical Study to Determine Bioequivalence Between Two Oral Medications of Empagliflozin/Metformin in 12.5 mg / 850 mg Tablets Under Fed Conditions. (clinicaltrials.gov) - P=N/A | N=42 | Completed | Sponsor: ADIUM

New trial

ACL24-PC018: Clinical Study to Determine Bioequivalence Between Two Oral Medications of Empagliflozin/Metformin in 5 mg / 850 mg Tablets Under Fed Conditions. (clinicaltrials.gov) - P=N/A | N=42 | Completed | Sponsor: ADIUM

New trial

ACL25-PC016: Clinical Study to Determine Bioequivalence Between Two Oral Medications of Empagliflozin/Metformin in 12.5 mg / 500 mg Tablets Under Fed Conditions. (clinicaltrials.gov) - P=N/A | N=42 | Completed | Sponsor: ADIUM

New trial