ReviewEuropean journal of pharmacology2019
SGLT2 inhibitors and metformin: Dual antihyperglycemic therapy and the risk of metabolic acidosis in type 2 diabetes.
Review in European journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 69 citations in OpenAlex.
- SGLT2 inhibition improves PI3Kα inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials.Breast cancer research and treatment · 2024Trial
- The effect of empagliflozin (sodium-glucose cotransporter-2 inhibitor) on osteoporosis and glycemic parameters in patients with type 2 diabetes: a quasi-experimental study.BMC musculoskeletal disorders · 2024Trial
- Real-world evidence of urinary tract infections and genital tract infections with sodium-glucose cotransporter-2 inhibitors (SGLT2i) alone or in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) in individuals with type-2 diabetes mellitus in India.BMC endocrine disorders · 2026Observational
- Empagliflozin modulates biofilm formation and virulence-associated gene expression in multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii.Archives of microbiology · 2026Article
- Severe Metabolic Acidosis Related to Simultaneous Use of Metformin and Dapagliflozin: A Case Report.Cureus · 2025Article
- The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study.Cardiovascular diabetology · 2025 · on this mapObservational
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- Risk of medication-induced lactic acidosis and hyperlactatemia: a pharmacovigilance study of the United States Food and Drug Administration's Adverse Event Reporting System database.Frontiers in pharmacology · 2025Article
- Cutaneous Adverse Drug Reactions Associated with SGLT2 Inhibitors.Journal of clinical medicine · 2024Review
- Urinary Tract Infections and Fungal Infections Associated with Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibitors and Metformin Combination: A Real-World Study from 2013 to 2023 Based on the FDA Adverse Event Reporting System (FAERS) Database.Journal of clinical practice and research · 2024Article
- Combined lactic acidosis and ketoacidosis in a female diabetic patient with severe heart failure.Cardiovascular endocrinology & metabolism · 2023Article
- Life-Threatening Acidosis With Metformin and Dapagliflozin Combination Therapy: A Case Report.Cureus · 2023Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Scientific and ethical issues in add-on designs for antidiabetic drugs.European journal of clinical pharmacology · 2022Article
- Canagliflozin-associated severe hyponatremia: a rare and potentially adverse effect?Endocrinology, diabetes & metabolism case reports · 2022Article
- Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis.Frontiers in pharmacology · 2022Article
- Metformin attenuates diabetic renal injury via the AMPK-autophagy axis.Experimental and therapeutic medicine · 2021Article
- Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system.Expert review of neurotherapeutics · 2021Article
- No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19.World journal of clinical cases · 2020Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The prevalence of type 2 diabetes mellitus (T2D) has risen in the United States and worldwide, with an increase in global prevalence from 4.7% to 8.5% between 1980 and 2014. A variety of antidiabetic drugs are available with different mechanisms of action, and multiple drugs are often used concomitantly to improve glycemic control. One of the newest classes of oral antihyperglycemic agents is the sodium glucose cotransporter-2 (SGLT2) inhibitors or "flozins". Recent clinical guidelines have suggested the use of SGLT2 inhibitors as add-on therapy in patients for whom metformin alone does not achieve glycemic targets, or as initial dual therapy with metformin in patients who present with higher glycated hemoglobin (HbA1c) levels. The FDA has approved fixed-dose combination (FDC) tablets with each of the three available SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) and metformin. Both drug classes are associated with the rare but serious life-threatening complications that result from metabolic acidosis, including lactic acidosis (with metformin) and euglycemic diabetic ketoacidosis (with SGLT2 inhibitors). This review summarizes the current literature on the pharmacokinetics and the molecular targets of metformin and SGLT2 inhibitors. It also addresses the common adverse effects and highlights the molecular mechanisms by which this dual antihyperglycemic therapy contributes to high anion gap metabolic acidosis. In conclusion, while the combination of metformin and SGLT2 inhibitors would be a better option in improving glycemic control with a low risk of hypoglycemia, an increase in the risk of metabolic acidosis during combination therapy may be borne in mind.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.