Research Article Details

Article ID: A42571
PMID: 34142426
Source: Diabetes Obes Metab
Title: Sodium-glucose cotransporter-2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews.
Abstract: AIMS: To summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus. MATERIALS AND METHODS: We searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431). RESULTS: We included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed "clear evidence of benefit" in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] -0.49% to -0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD -1.09 kg to -2.99 kg). "Possible benefit" was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all-cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed "clear evidence of no effect or equivalence" in relation to stroke and fractures. "Clear evidence of harm" was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found "no conclusions possible due to lack of evidence". CONCLUSIONS: Our results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.
DOI: 10.1111/dom.14470

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T02 Sodium/glucose cotransporter 2 SLC5A2 inhibitor Transporter P31639 SC5A2_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T21 Diacylglycerol O-acyltransferase 2 DGAT2 inhibitor Enzyme Q96PD7 DGAT2_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I08 114 Cardiovascular system disease A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system disease of anatomical entity Details
I09 104 Bacterial infectious disease A disease by infectious agent that results_in infection, has_material_basis_in Bacteria. http://en.wikipedia.org/wiki/Pathogenic_bacteria disease by infectious agent Details
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I16 6713 Cerebrovascular disease An vascular disease that is characterized by dysfunction of the blood vessels supplying the brain. http://en.wikipedia.org/wiki/Cerebrovascular_disease, http://www.ncbi.nlm.nih.gov/books/NBK378/ disease of anatomical entity/ cardiovascular system disease/ vascular disease/cerebrovascular disease Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D549 SGLT2 inhibitor Chemical drug -- SGLT2 inhibitor -- Under clinical trials Details
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D248 Obeticholic Acid Chemical drug DB05990 NR1H4 activator; NR1H4 agonist; FXR agonist Enhance lipid metabolism Approval rejected Details
D094 Cysteamine Chemical drug DB00847 GSS stimulant Renal drug Under clinical trials Details
D095 Cysteamine bitartrate Chemical drug DB00847 -- -- Under clinical trials Details