{ "release_id": "f6f6f1b6f50379ed", "id": "cardio:sglt2-inhibitors", "owner": "cardio", "kind": "drug", "slug": "sglt2-inhibitors", "name": "SGLT2 inhibitors (drug class)", "aliases": [ "Sodium-glucose cotransporter 2 inhibitors" ], "atlases": [ "cardio" ], "summary_plain": "A group of pills that a US government patient page says were approved for diabetes because they lower blood sugar. Four trials in this atlas tested dapagliflozin or empagliflozin in adults with heart failure. In each, the drug group had a lower rate than the placebo group of cardiovascular death or worsening heart failure. The abstracts report the results in people with and without diabetes. Two of the trials enrolled people with an ejection fraction of 40% or less and two enrolled people above 40%.", "summary_technical": "US drug-label classes in RxClass for dapagliflozin and empagliflozin: mechanism-of-action class Sodium-Glucose Transporter 2 Inhibitors and established pharmacologic class Sodium-Glucose Cotransporter 2 Inhibitor. The MeSH heading D000077203 is an exact match. This is the shared class page: the diabetes and kidney trials of the same medicines sit in other areas of the atlas. Class-level results are a side-by-side list of four trial results and not a pooled analysis.", "editorial_state": "draft", "last_substantive_edit": "2026-10-15", "last_evidence_check": "2026-10-14", "next_review_due": null, "identifiers": [ { "scheme": "mesh", "value": "D000077203", "normalized_value": "D000077203", "match": "exact", "version": "read 2026-10-14", "label": null, "from_source": false } ], "navigation": { "cardio": { "system": [ "heart" ], "condition-area": [ "heart-failure", "diabetes-and-metabolic-disease", "kidney-connections" ] } }, "payload": { "level": "class", "mechanism": "The US drug-label mechanism-of-action class for dapagliflozin and empagliflozin in RxClass is Sodium-Glucose Transporter 2 Inhibitors." }, "content_digest": "1807cceaa5a9e58a1aa4bc1efb3ec1c54ad8cc30f961cbab1077ee8ecc4a862d", "review": { "content_digest": "1807cceaa5a9e58a1aa4bc1efb3ec1c54ad8cc30f961cbab1077ee8ecc4a862d", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "claims": [ { "release_id": "f6f6f1b6f50379ed", "id": "cardio:claim-aha-acc-hfsa-2022-sglt2i-hfref", "owner": "cardio", "subject_entity_id": "cardio:sglt2-inhibitors", "category": "recommendation", "statement": "An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says that in symptomatic patients with chronic heart failure with reduced ejection fraction, an SGLT2 inhibitor is recommended in order to cut hospital admissions and cardiovascular death, whether or not the patient has type 2 diabetes. It prints the class of recommendation as 1a. It adds that SGLT2 inhibitors can also be beneficial in heart failure with mildly reduced or preserved ejection fraction, at class 2a.", "context": { "id": "cardio:ctx-aha-acc-hfsa-2022-symptomatic-chronic-hfref", "label": "Symptomatic patients with chronic HFrEF (2022 AHA/ACC/HFSA, as summarized by the ACC)", "recipient": "unknown", "population": "Symptomatic patients with chronic heart failure with reduced ejection fraction (ejection fraction of 40% or less), with or without type 2 diabetes, as the ACC summary words the SGLT2 inhibitor statement. The summary gives no age limits.", "care_setting": "Not stated in the ACC summary.", "geography": "Not stated in the ACC summary (issued by American societies; jurisdiction not verified)", "life_stage_note": "Not stated in the ACC summary", "life_stage_terms": null, "gestational_age_min_days": null, "gestational_age_max_days": null, "gestational_age_basis": null, "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "Not applicable (guideline context)", "eligibility": { "inclusion": [ "Symptomatic chronic heart failure with an ejection fraction of 40% or less", "With or without type 2 diabetes" ], "exclusion": [] } }, "evidence_stage": "guidance", "certainty": "not_assessed", "certainty_method": null, "limitations": "The class of recommendation is as printed on the ACC page. The class 2a statement for mildly reduced and preserved ejection fraction is a different population from this claim context and is not a recommendation record here. The source is the ACC summary, not the guideline text. PubMed lists three corrections to the guideline; their text was not read, so it is not known whether they change anything stated here.", "editorial_state": "draft", "checked_at": "2026-10-15", "next_review_due": null, "valid_from": null, "valid_to": null, "citations": [ { "evidence_role": "supports", "locator": "Key perspective 3, sentence 2, fragments 1 and 2", "applicability_note": "SGLT2 inhibitor recommended in symptomatic chronic HFrEF, with or without type 2 diabetes.", "snapshot": { "id": "cardio:acc-hf2022-key-perspectives-2026-10-15", "retrieved_at": "2026-10-15T13:50:22Z", "content_hash": "9bf3f8d91011b793cc049e80db09ae5624271eb6cdb688f5331c7f8aa1556cad", "source_effective_date": null, "public_archive_url": null, "source_state": "corrected" }, "source": { "id": "cardio:aha-acc-hfsa-2022-heart-failure", "source_type": "guideline", "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines", "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063", "identifiers": [ { "scheme": "doi", "value": "10.1161/CIR.0000000000001063", "normalized_value": "10.1161/cir.0000000000001063", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "35363499", "normalized_value": "35363499", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2022-05-03", "publisher": "Circulation", "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.", "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed. ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.", "public_text": "cite_only" } }, { "evidence_role": "supports", "locator": "Key perspective 3, sentence 3", "applicability_note": "Class 2a for mildly reduced and preserved ejection fraction.", "snapshot": { "id": "cardio:acc-hf2022-key-perspectives-2026-10-15", "retrieved_at": "2026-10-15T13:50:22Z", "content_hash": "9bf3f8d91011b793cc049e80db09ae5624271eb6cdb688f5331c7f8aa1556cad", "source_effective_date": null, "public_archive_url": null, "source_state": "corrected" }, "source": { "id": "cardio:aha-acc-hfsa-2022-heart-failure", "source_type": "guideline", "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines", "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063", "identifiers": [ { "scheme": "doi", "value": "10.1161/CIR.0000000000001063", "normalized_value": "10.1161/cir.0000000000001063", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "35363499", "normalized_value": "35363499", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2022-05-03", "publisher": "Circulation", "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.", "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed. ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.", "public_text": "cite_only" } }, { "evidence_role": "context", "locator": "Key perspective 1, classification list (HFrEF)", "applicability_note": "HFrEF means an ejection fraction of 40% or less.", "snapshot": { "id": "cardio:acc-hf2022-key-perspectives-2026-10-15", "retrieved_at": "2026-10-15T13:50:22Z", "content_hash": "9bf3f8d91011b793cc049e80db09ae5624271eb6cdb688f5331c7f8aa1556cad", "source_effective_date": null, "public_archive_url": null, "source_state": "corrected" }, "source": { "id": "cardio:aha-acc-hfsa-2022-heart-failure", "source_type": "guideline", "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines", "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063", "identifiers": [ { "scheme": "doi", "value": "10.1161/CIR.0000000000001063", "normalized_value": "10.1161/cir.0000000000001063", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "35363499", "normalized_value": "35363499", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2022-05-03", "publisher": "Circulation", "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.", "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed. ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.", "public_text": "cite_only" } }, { "evidence_role": "context", "locator": "CommentsCorrectionsList, three ErratumIn entries", "applicability_note": "Shows that corrections exist. What they change is unknown.", "snapshot": { "id": "cardio:pubmed-35363499-2026-10-15", "retrieved_at": "2026-10-15T13:48:58Z", "content_hash": "359253a28c2add87ff845ef77e0400c1886971358eacddb04f09833df0707f1f", "source_effective_date": null, "public_archive_url": null, "source_state": "corrected" }, "source": { "id": "cardio:aha-acc-hfsa-2022-heart-failure", "source_type": "guideline", "title": "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines", "canonical_url": "https://doi.org/10.1161/CIR.0000000000001063", "identifiers": [ { "scheme": "doi", "value": "10.1161/CIR.0000000000001063", "normalized_value": "10.1161/cir.0000000000001063", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "35363499", "normalized_value": "35363499", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2022-05-03", "publisher": "Circulation", "edition": "Published in Circulation 145(18):e895-e1032 (issue date 2022-05-03; electronic publication 2022-04-01). PubMed abstract and bibliographic data only. PubMed lists no PMC copy. The guideline text was not read. PubMed lists 3 corrections to the guideline; their text was not read. The same source also holds a snapshot of the ACC key-perspectives summary page of the guideline (dated Apr 01, 2022), which is an ACC summary and not the guideline text. The recommendation text for this atlas comes from that page. The publisher field is the journal title as PubMed gives it.", "reuse_basis": "PubMed record and ACC page. PubMed record fetched through NCBI E-utilities on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. Bibliographic metadata and short quotations from the PubMed abstract, under 25 words each. The full text was not redistributed and the societies' reuse terms were not reviewed. ACC web page fetched with a plain Mozilla/5.0 user agent on 2026-10-15. Only the hash of the bytes is kept; nothing is committed. The ACC's reuse terms were not read, so public text is cite_only: public pages state the summary in the atlas's own words, with a citation and a link, and use no ACC wording. Quote rows are short evidence fragments for the reviewer.", "public_text": "cite_only" } } ], "review": { "content_digest": "be665464acb8f4d2b1fa1f4c30a14718c1f7cf96befaf5ca2a5c2ba859ca4361", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "api_path": "api/v1/claims/cardio--claim-aha-acc-hfsa-2022-sglt2i-hfref.json" }, { "release_id": "f6f6f1b6f50379ed", "id": "cardio:claim-sglt2-hf-four-trials", "owner": "cardio", "subject_entity_id": "cardio:sglt2-inhibitors", "category": "effect", "statement": "In four separate placebo-controlled trials in adults with chronic heart failure, the primary outcome was lower with an SGLT2 inhibitor than with placebo. The primary outcome was a composite of cardiovascular death and worsening heart failure, defined slightly differently in each trial. The hazard ratios (95% confidence intervals) were: DAPA-HF, dapagliflozin, ejection fraction 40% or less, 0.74 (0.65 to 0.85); EMPEROR-Reduced, empagliflozin, 40% or less, 0.75 (0.65 to 0.86); EMPEROR-Preserved, empagliflozin, above 40%, 0.79 (0.69 to 0.90); DELIVER, dapagliflozin, above 40%, 0.82 (0.73 to 0.92). The abstracts report the benefit or its consistency in people with and without diabetes. In DELIVER, cardiovascular death on its own had a hazard ratio of 0.88 (0.74 to 1.05), and in EMPEROR-Preserved the effect was mainly related to fewer hospitalizations for heart failure. This lists four trial results side by side. It is not a pooled analysis.", "context": { "id": "cardio:ctx-sglt2-hf-four-trials", "label": "Adults with chronic heart failure in four placebo-controlled SGLT2 inhibitor trials, ejection fraction 40% or less in two and above 40% in two", "recipient": "adult", "population": "Adults with chronic heart failure in four separate trials: DAPA-HF and EMPEROR-Reduced (ejection fraction of 40% or less) and EMPEROR-Preserved and DELIVER (ejection fraction of more than 40%). Each trial added the SGLT2 inhibitor or placebo to recommended or usual therapy. The abstracts say findings were similar or consistent in people with and without diabetes. This context joins four trials for comparison and is not a pooled analysis.", "care_setting": "Not stated in the abstract. The registry record is not read for setting.", "geography": "Multinational trials.", "life_stage_note": "Adults.", "life_stage_terms": null, "gestational_age_min_days": null, "gestational_age_max_days": null, "gestational_age_basis": null, "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "Median follow-up differs by trial: 18.2 months, 16 months, 26.2 months and 2.3 years (abstracts).", "eligibility": { "inclusion": [ "Chronic heart failure", "Ejection fraction of 40% or less (two trials) or more than 40% (two trials)" ], "exclusion": [ "Entry and exclusion rules differ by trial and were not read in full" ] } }, "evidence_stage": "interventional", "certainty": "not_assessed", "certainty_method": null, "limitations": "The hazard ratios are the trials' own and were not pooled or re-analysed. The trials differ in entry criteria, in the drug, in the definition of the primary outcome and in follow-up. All four were funded by the drug makers. Numbers come from the PubMed abstracts; full texts were not read. Harms differ by trial and are given on the trial claims (genital and urinary tract infections and low blood pressure with empagliflozin in EMPEROR-Preserved; genital tract infection with empagliflozin in EMPEROR-Reduced). No certainty rating was assessed.", "editorial_state": "draft", "checked_at": "2026-10-14", "next_review_due": null, "valid_from": null, "valid_to": null, "citations": [ { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 1", "applicability_note": "DAPA-HF primary outcome. Abstract of the paper from PubMed; the full text was not read.", "snapshot": { "id": "cardio:pubmed-31535829-2026-10-14", "retrieved_at": "2026-10-14T18:18:44Z", "content_hash": "d86f142d100d12573e1bc9993fbf40729a81ab213219aa50b1d716709bcb2b4c", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "cardio:pubmed-10-1056-nejmoa1911303", "source_type": "publication", "title": "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction", "canonical_url": "https://doi.org/10.1056/NEJMoa1911303", "identifiers": [ { "scheme": "doi", "value": "10.1056/NEJMoa1911303", "normalized_value": "10.1056/nejmoa1911303", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "31535829", "normalized_value": "31535829", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2019-11-21", "publisher": "The New England journal of medicine", "edition": "PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.", "reuse_basis": "PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 4", "applicability_note": "DAPA-HF: diabetes and no diabetes. Abstract of the paper from PubMed; the full text was not read.", "snapshot": { "id": "cardio:pubmed-31535829-2026-10-14", "retrieved_at": "2026-10-14T18:18:44Z", "content_hash": "d86f142d100d12573e1bc9993fbf40729a81ab213219aa50b1d716709bcb2b4c", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "cardio:pubmed-10-1056-nejmoa1911303", "source_type": "publication", "title": "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction", "canonical_url": "https://doi.org/10.1056/NEJMoa1911303", "identifiers": [ { "scheme": "doi", "value": "10.1056/NEJMoa1911303", "normalized_value": "10.1056/nejmoa1911303", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "31535829", "normalized_value": "31535829", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2019-11-21", "publisher": "The New England journal of medicine", "edition": "PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.", "reuse_basis": "PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 1", "applicability_note": "EMPEROR-Reduced primary outcome. Abstract of the paper from PubMed; the full text was not read.", "snapshot": { "id": "cardio:pubmed-32865377-2026-10-14", "retrieved_at": "2026-10-14T18:18:45Z", "content_hash": "6519ae8338ccd9e7fb161e306e177ad9a66f171c96ee4da655099894e0ff9ea8", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "cardio:pubmed-10-1056-nejmoa2022190", "source_type": "publication", "title": "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure", "canonical_url": "https://doi.org/10.1056/NEJMoa2022190", "identifiers": [ { "scheme": "doi", "value": "10.1056/NEJMoa2022190", "normalized_value": "10.1056/nejmoa2022190", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "32865377", "normalized_value": "32865377", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2020-10-08", "publisher": "The New England journal of medicine", "edition": "PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.", "reuse_basis": "PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 2", "applicability_note": "EMPEROR-Reduced: consistency with and without diabetes. Abstract of the paper from PubMed; the full text was not read.", "snapshot": { "id": "cardio:pubmed-32865377-2026-10-14", "retrieved_at": "2026-10-14T18:18:45Z", "content_hash": "6519ae8338ccd9e7fb161e306e177ad9a66f171c96ee4da655099894e0ff9ea8", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "cardio:pubmed-10-1056-nejmoa2022190", "source_type": "publication", "title": "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure", "canonical_url": "https://doi.org/10.1056/NEJMoa2022190", "identifiers": [ { "scheme": "doi", "value": "10.1056/NEJMoa2022190", "normalized_value": "10.1056/nejmoa2022190", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "32865377", "normalized_value": "32865377", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2020-10-08", "publisher": "The New England journal of medicine", "edition": "PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched.", "reuse_basis": "PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.", "public_text": "quote" } }, { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 1", "applicability_note": "EMPEROR-Preserved primary outcome. 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