Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States

Classified as probably not a substantial claim.

SGLT2i and GLP-1RA are recommended in patients with CKD with type 2 diabetes by the American Diabetes Association and KDIGO clinical guidelines.

“Sodium/glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) are recommended in patients with CKD with type 2 diabetes by the American Diabetes Association and KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines.15,16”

• cites [15] American Diabetes Association Professional Practice Committee 11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes—2022 Diabetes Care 45 suppl 1 2022 S175 S184 34964873 sourcePartly supported

  The Introduction (page unavailable) says the American Diabetes Association recommends SGLT2 inhibitors for patients with diabetes and CKD. It does not state that GLP-1 receptor agonists are recommended for these patients or attribute either recommendation to KDIGO; it names an American College of Cardiology statement instead. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [16] Diabetes in CKD KDIGO https://kdigo.org/guidelines/diabetes-ckd/ sourceCould not verify

  The annual report passage describing its scope (section titled “US Renal Data System 2020 Annual Data Report,” page unavailable) concerns CKD surveillance, not treatment recommendations. Searches for SGLT2 inhibitors, GLP-1 receptor agonists, and ADA or KDIGO guidelines found no passage in our copy addressing the claimed recommendations. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Elixhauser Comorbidity Index includes 30 comorbid condition measures and has been used to assess prevalent comorbid conditions in health research for examining medication use.

“The Elixhauser Comorbidity Index includes a comprehensive set of 30 comorbid condition measures (covering acute and chronic conditions) and has been used to assess prevalent comorbid conditions in health research for examining medication use.18,22”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source
• cites [22] Nathan A.S. Geng Z. Dayoub E.J. Racial, ethnic, and socioeconomic inequities in the prescription of direct oral anticoagulants in patients with venous thromboembolism in the United States Circ Cardiovasc Qual Outcomes 12 2019 e005600 10.1161/CIRCOUTCOMES.119.005600 PMC9119738 30950652 sourceCould not verify

  The Introduction describes assessing comorbidities in a study of glucose-lowering medication choice, but names the Diabetes Complications Severity Index and selected individual conditions, not the Elixhauser Comorbidity Index. Searches for “Elixhauser” and “30 comorbid condition measures” found no passage addressing the index’s composition or its use for this purpose. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Studies have shown that racial disparity persists at all levels of social economic status.

“Similar to our finding, studies have shown that racial disparity persists at all levels of social economic status.26,27”

• cites [26] Williams D.R. Mohammed S.A. Leavell J. Collins C. Race, socioeconomic status, and health: complexities, ongoing challenges, and research opportunities Ann N Y Acad Sci 1186 2010 69 101 10.1111/j.1749-6632.2009.05339.x 20201869 PMC3442603 sourcePartly supported

  The report’s introductory section describes racial and ethnic disparities in kidney-disease care and outcomes and says a chapter examines social determinants of health. Neither that passage nor the Notes About Race and Ethnicity establishes that disparities persist at all socioeconomic levels; searches for socioeconomic status, income, and education found no such comparison in our copy. Page numbers are unavailable. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [27] Braveman P.A. Cubbin C. Egerter S. Williams D.R. Pamuk E. Socioeconomic disparities in health in the United States: what the patterns tell us Am J Public Health 100 suppl 1 2010 S186 S196 10.2105/AJPH.2009.166082 20147693 PMC2837459 sourcePartly supported

  The Results (Table 4; page unavailable) report higher hypoglycemia risk for Black than White patients and include low-income subsidy status as a socioeconomic measure. That adjusted finding supports a racial disparity, but the paper does not show that it persists at all socioeconomic levels. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A published study in the non-CKD population reported that women were more likely to start a GLP-1RA than men but were less likely to start SGLT2i.

“A published study in the non-CKD population reported a similar finding that women were more likely to start a GLP-1RA than men but were less likely to start SGLT2i.25”

• cites [25] McCoy R.G. Van Houten H.K. Karaca-Mandic P. Ross J.S. Montori V.M. Shah N.D. Second-line therapy for type 2 diabetes management: the treatment/benefit paradox of cardiovascular and kidney comorbidities Diabetes Care 44 2021 2302 2311 10.2337/dc20-2977 34348996 PMC8929191 sourceCould not verify

  The Results (Cohort Characteristics; page unavailable) and Discussion address kidney-function decline, not initiation of diabetes medications. A search for GLP-1RA, SGLT2i, and sex differences in their initiation found no passage addressing the claim. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Several prior studies in patients without CKD have demonstrated lower use of these agents among Black patients.

“Several prior studies in patients without CKD have demonstrated lower use of these agents among Black patients.18,24,25”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source
• cites [24] McCoy R.G. Dykhoff H.J. Sangaralingham L. Adoption of new glucose-lowering medications in the U.S. - the case of SGLT2 inhibitors: nationwide cohort study Diabetes Technol Ther 21 2019 702 712 10.1089/dia.2019.0213 31418588 PMC7207017 sourceNot checked — no full text of the source
• cites [25] McCoy R.G. Van Houten H.K. Karaca-Mandic P. Ross J.S. Montori V.M. Shah N.D. Second-line therapy for type 2 diabetes management: the treatment/benefit paradox of cardiovascular and kidney comorbidities Diabetes Care 44 2021 2302 2311 10.2337/dc20-2977 34348996 PMC8929191 sourceCould not verify

  The Results and Discussion (pages not provided) compare kidney-function decline in Black and White adults with largely preserved kidney function, but do not report lower use of the agents among Black patients. Searches for racial differences in medication use, including ACE inhibitors and antihypertensive treatment, found no passage addressing the claim. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

May combine two claims.

Clinical studies have demonstrated the cardiovascular and kidney benefits of SGLT2i and GLP-1RA, especially the CREDENCE and DAPA-CKD trials, which were specially designed to focus on patients with CKD.

“Clinical studies have demonstrated the cardiovascular and kidney benefits of SGLT2i and GLP-1RA, especially the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) and the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trials, which were specially designed to focus on patients with CKD.6,8”

• cites [6] Mahaffey K.W. Jardine M.J. Bompoint S. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups Circulation 140 2019 739 750 10.1161/CIRCULATIONAHA.119.042007 31291786 PMC6727954 sourcePartly supported

  The Abstract (p. 1437) identifies DAPA-CKD as a trial designed for patients with chronic kidney disease and reports kidney and cardiovascular benefits of the SGLT2 inhibitor dapagliflozin. The Discussion also reports kidney-protective effects from CREDENCE. This paper does not address GLP-1 receptor agonist benefits, so it does not support that part of the sentence. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [8] Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. Dapagliflozin in patients with chronic kidney disease N Engl J Med 383 2020 1436 1446 10.1056/NEJMoa2024816 32970396 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Our research team showed that Medicare-enrolled Black patients with CKD had a higher risk of developing hypoglycemia than White patients.

“Our research team showed that Medicare-enrolled Black patients with CKD had a higher risk of developing hypoglycemia than White patients.30”

• cites [30] Zhao J.Z. Weinhandl E.D. Carlson A.M. St. Peter W.L. Hypoglycemia risk with SGLT2 inhibitors or glucagon-like peptide 1 receptor agonists versus sulfonylureas among medicare insured adults with CKD in the United States Kidney Med 4 2022 100510 10.1016/j.xkme.2022.100510 PMC9310119 35898692 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The US Renal Data System annual data reported that Black patients had the highest prevalence of end-stage kidney disease in racial and ethnic groups from 2000 to 2019.

“The US Renal Data System annual data reported that Black patients had the highest prevalence of end-stage kidney disease in racial and ethnic groups from 2000 to 2019.29”

• cites [29] Johansen K.L. Chertow G.M. Gilbertson D.T. US Renal Data System 2021 Annual Data Report: epidemiology of kidney disease in the United States Am J Kidney Dis 79 4 suppl 1 2022 A8 A12 10.1053/j.ajkd.2022.02.001 35331382 PMC8935019 sourceCould not verify

  The Methods and Results describe a 2019 analysis of Medicare Part D drug coverage and costs, not end-stage kidney disease prevalence. Searches for the US Renal Data System and for racial differences in kidney disease prevalence found no relevant passage in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Health disparities in Black patients with diabetes and CKD have been well documented.

“Health disparities in Black patients with diabetes and CKD have been well documented.”

• cites [28] Peralta C.A. Vittinghoff E. Bansal N. Trajectories of kidney function decline in young black and white adults with preserved GFR: results from the Coronary Artery Risk Development in Young Adults (CARDIA) study Am J Kidney Dis 62 2013 261 266 10.1053/j.ajkd.2013.01.012 23473985 PMC3714331 sourceCould not verify

  The paper’s Abstract discusses diabetes, CKD, and SGLT2 inhibitors, but not health disparities in Black patients. Searches for Black patients, African Americans, and racial disparities found no passage addressing the claim; no page numbers are available in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [29] Johansen K.L. Chertow G.M. Gilbertson D.T. US Renal Data System 2021 Annual Data Report: epidemiology of kidney disease in the United States Am J Kidney Dis 79 4 suppl 1 2022 A8 A12 10.1053/j.ajkd.2022.02.001 35331382 PMC8935019 sourceCould not verify

  The Methods and Discussion address Medicare Part D coverage and out-of-pocket costs for diabetes medications, not disparities among Black patients with diabetes and CKD. Searches for Black patients, racial disparities, and CKD found no passage in our copy addressing the claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [30] Zhao J.Z. Weinhandl E.D. Carlson A.M. St. Peter W.L. Hypoglycemia risk with SGLT2 inhibitors or glucagon-like peptide 1 receptor agonists versus sulfonylureas among medicare insured adults with CKD in the United States Kidney Med 4 2022 100510 10.1016/j.xkme.2022.100510 PMC9310119 35898692 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The Coronary Artery Risk Development in Young Adults study found that Black patients had significantly faster annualized estimated glomerular filtration rates of decline.

“The Coronary Artery Risk Development in Young Adults study found that Black patients had significantly faster annualized estimated glomerular filtration rates of decline.28”

• cites [28] Peralta C.A. Vittinghoff E. Bansal N. Trajectories of kidney function decline in young black and white adults with preserved GFR: results from the Coronary Artery Risk Development in Young Adults (CARDIA) study Am J Kidney Dis 62 2013 261 266 10.1053/j.ajkd.2013.01.012 23473985 PMC3714331 sourceCould not verify

  The paper’s Abstract discusses SGLT2 inhibitors, urinary tract infections, and kidney protection, but does not report findings from the Coronary Artery Risk Development in Young Adults study. Searches for that study and for racial differences in annualized eGFR decline found no relevant passage in our copy. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

May combine two claims.

Canagliflozin was included on <75% of Part D plan formularies in 2019 and 2020, but coverage without prior authorization and without step therapy requirements was only 53.2% in 2019 Part D plans.

“Canagliflozin was included on <75% of Part D plan formularies in 2019 and 2020,32,33 but coverage without prior authorization and without step therapy requirements was only 53.2% (95% CI, 49.1%-57.4%) in 2019 Part D plans.32”

• cites [32] Luo J. Feldman R. Rothenberger S.D. Hernandez I. Gellad W.F. Coverage, formulary restrictions, and out-of-pocket costs for sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in the Medicare Part D program JAMA Netw Open 3 2020 e2020969 10.1001/jamanetworkopen.2020.20969 PMC7563069 33057641 sourceNot checked — no full text of the source
• cites [33] Part D plans generally include drugs commonly used by dual eligibles: 2020. US Department of Health and Human Services Office of Inspector General. Accessed May 11, 2022. https://oig.hhs.gov/oei/reports/oei-05-20-00190.asp sourceCould not verify

  The Discussion addresses disparities in Medicare home health care, not prescription-drug coverage. Searches of our copy for canagliflozin, Part D formularies, prior authorization, step therapy, and the 53.2% figure found no passage addressing the claim. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The concern that SGLT2i increase risk of UTIs has been refuted in a recent meta-analysis.

“but this has been refuted in a recent meta-analysis.31”

• cites [31] Sarafidis P.A. Ortiz A. The risk for urinary tract infections with sodium-glucose cotransporter 2 inhibitors: no longer a cause of concern? Clin Kidney J 13 2020 24 26 10.1093/ckj/sfz170 32082549 PMC7025347 sourceCould not verify

  The Discussion addresses acute kidney injury, not urinary tract infections, and the Methods describe an analysis of the DECLARE–TIMI 58 randomised trial rather than a meta-analysis. Searches for urinary tract infection, UTI, and meta-analysis found no passage in our copy addressing whether SGLT2 inhibitors increase UTI risk. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Medicare claims data sources of race/ethnicity information are commonly used in reports and studies of health disparities.

“Further, although Medicare claims that data sources of race/ethnicity information are commonly used in reports and studies of health disparities,35,36 Jarrín et al37 suggested high validity for Black patients and low sensitivity for Hispanic and Asian patients in Medicare beneficiary data files.”

• cites [35] Figueroa J.F. Zhou X. Jha A.K. Characteristics and spending patterns of persistently high-cost medicare patients Health Aff (Millwood) 38 2019 107 114 10.1377/hlthaff.2018.05160 30615516 sourceNot checked — no full text of the source
• cites [36] Joynt Maddox K.E. Chen L.M. Zuckerman R. Epstein A.M. Association between race, neighborhood, and Medicaid enrollment and outcomes in Medicare home health care J Am Geriatr Soc 66 2018 239 246 10.1111/jgs.15082 28975604 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Significant benefits of SGLT2i were shown among the subgroup patients (aged ≥65 years) in the study of EMPAREG, CANVAS, DECLARE, and DAPA-CKD.

“However, significant benefits of SGLT2i were shown among the subgroup patients (aged greater than or equal to 65 years) in the study of EMPAREG, CANVAS, DECLARE, and DAPA-CKD.6, 7, 8,11,12,34”

• cites [6] Mahaffey K.W. Jardine M.J. Bompoint S. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups Circulation 140 2019 739 750 10.1161/CIRCULATIONAHA.119.042007 31291786 PMC6727954 sourceSupported
• cites [7] Wiviott S.D. Raz I. Bonaca M.P. Dapagliflozin and cardiovascular outcomes in type 2 diabetes N Engl J Med 380 2019 347 357 10.1056/NEJMoa1812389 30415602 sourceNot checked — no full text of the source
• cites [8] Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. Dapagliflozin in patients with chronic kidney disease N Engl J Med 383 2020 1436 1446 10.1056/NEJMoa2024816 32970396 sourceNot checked — no full text of the source
• cites [11] Wanner C. Inzucchi S.E. Lachin J.M. Empagliflozin and progression of kidney disease in type 2 diabetes N Engl J Med 375 2016 323 334 10.1056/NEJMoa1515920 27299675 sourcePartly supported

  The Discussion describes cardiovascular benefits in the EMPA-REG OUTCOME trial of the SGLT2 inhibitor empagliflozin. It does not report whether those benefits were significant among patients aged 65 or older, or address the claimed subgroup findings in CANVAS, DECLARE, or DAPA-CKD. No page number is available in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [12] Zinman B. Wanner C. Lachin J.M. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes N Engl J Med 373 2015 2117 2128 10.1056/NEJMoa1504720 26378978 sourcePartly supported

  The Conclusions mention improved cardiovascular outcomes in a trial of the SGLT2 inhibitor empagliflozin among high-risk patients with type 2 diabetes. They do not report benefits specifically for patients aged ≥65 or findings from CANVAS, DECLARE, or DAPA-CKD; this paper’s own trial tested semaglutide. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [34] Mosenzon O. Wiviott S.D. Cahn A. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial Lancet Diabetes Endocrinol 7 2019 606 617 10.1016/S2213-8587(19)30180-9 31196815 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Approximately 75% of Medicare beneficiaries with CKD were enrolled in Medicare Part D in 2019.

“However, approximately 75% of Medicare beneficiaries with CKD were enrolled in Medicare Part D in 2019.29”

• cites [29] Johansen K.L. Chertow G.M. Gilbertson D.T. US Renal Data System 2021 Annual Data Report: epidemiology of kidney disease in the United States Am J Kidney Dis 79 4 suppl 1 2022 A8 A12 10.1053/j.ajkd.2022.02.001 35331382 PMC8935019 sourceCould not verify

  The Methods describe a 2019 analysis of Medicare Part D drug plans, weighted by plan enrollment, but do not report the proportion of beneficiaries with CKD enrolled in Part D. Searches for CKD, chronic kidney disease, and approximately 75% found no passage addressing that statistic; page numbers were not available in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Zip code-level household data are commonly used in Medicare studies.

“Zip code–level household data are commonly used in Medicare studies.18,22”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source
• cites [22] Nathan A.S. Geng Z. Dayoub E.J. Racial, ethnic, and socioeconomic inequities in the prescription of direct oral anticoagulants in patients with venous thromboembolism in the United States Circ Cardiovasc Qual Outcomes 12 2019 e005600 10.1161/CIRCOUTCOMES.119.005600 PMC9119738 30950652 sourceCould not verify

  The Introduction describes claims data for commercial and Medicare Advantage enrollees and lists patient demographics, but does not mention ZIP code–level household data. Searches for ZIP code, household income, and census data found no passage addressing whether such data are commonly used in Medicare studies. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Jarrín et al suggested high validity for Black patients and low sensitivity for Hispanic and Asian patients in Medicare beneficiary data files.

“Further, although Medicare claims that data sources of race/ethnicity information are commonly used in reports and studies of health disparities,35,36 Jarrín et al37 suggested high validity for Black patients and low sensitivity for Hispanic and Asian patients in Medicare beneficiary data files.”

• cites [37] Jarrín O.F. Nyandege A.N. Grafova I.B. Dong X. Lin H. Validity of race and ethnicity codes in Medicare administrative data compared with gold-standard self-reported race collected during routine home health care visits Med Care 58 2020 e1 e8 10.1097/MLR.0000000000001216 31688554 PMC6904433 sourcePartly supported

  The Results (page not provided) report high sensitivity and specificity for identifying Black beneficiaries with both Medicare race variables. They report low Hispanic sensitivity for the EDB variable (36.2), but good sensitivity for the RTI variable (90.8); sensitivity for Asian/Pacific Islander beneficiaries is 62.6 and 74.7, respectively. The claim omits these differences between the data files, particularly for Hispanic beneficiaries. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

The clinical trials that may have impacted our results were CANVAS, EMPA-REG OUTCOME, SUSTAIN-6, and LEADER, all of which demonstrated significant cardiovascular and kidney benefits of SGLT-2i and GLP-1RA.

“The clinical trials that may have impacted our results were the CANVAS (canagliflozin, published 2017), EMPA-REG OUTCOME (empagliflozin, 2015), the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial (semaglutide, 2016), and the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEAD”

• cites [5] Neal B. Perkovic V. Mahaffey K.W. Canagliflozin and cardiovascular and renal events in type 2 diabetes N Engl J Med 377 2017 644 657 10.1056/NEJMoa1611925 28605608 sourcePartly supported

  The Trial Design and Oversight section says EMPA-REG OUTCOME findings prompted a change to this paper’s trial protocol. The Discussion describes cardiovascular and renal benefits in prior SGLT2-inhibitor trials, including trials with empagliflozin and canagliflozin. Our copy does not establish the claimed benefits for SUSTAIN-6 or LEADER, or say that all four trials affected the citing authors’ results. Page numbers were not available in the indexed passages. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [11] Wanner C. Inzucchi S.E. Lachin J.M. Empagliflozin and progression of kidney disease in type 2 diabetes N Engl J Med 375 2016 323 334 10.1056/NEJMoa1515920 27299675 sourceSupported
• cites [12] Zinman B. Wanner C. Lachin J.M. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes N Engl J Med 373 2015 2117 2128 10.1056/NEJMoa1504720 26378978 sourcePartly supported

  The Conclusions identify this paper as SUSTAIN-6 and report a significantly lower composite cardiovascular-event rate with semaglutide. The results also report significantly less new or worsening nephropathy. The paper does not establish kidney benefits for all four named trials or whether those trials affected the citing authors’ results. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [13] Marso S.P. Daniels G.H. Brown-Frandsen K. Liraglutide and cardiovascular outcomes in type 2 diabetes N Engl J Med 375 2016 311 322 10.1056/NEJMoa1603827 27295427 PMC4985288 sourceSupported
• cites [14] Marso S.P. Bain S.C. Consoli A. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes N Engl J Med 375 2016 1834 1844 10.1056/NEJMoa1607141 27633186 sourcePartly supported

  The Discussion (page not provided) reports cardiovascular and kidney benefits from EMPA-REG OUTCOME, CANVAS, and LEADER. It does not discuss SUSTAIN-6 trial outcomes or establish that these trials affected the citing authors’ results; its mention of semaglutide concerns FDA approval in 2019. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Among the cohort, 10.0% had an initiating prescription for SGLT2i, 17.4% for GLP-1RA, and 72.6% for sulfonylureas.

“of whom 10.0% (n = 5,277) had an initiating prescription for SGLT2i, 17.4% (n = 9,252) for GLP-1RA, and 72.6% (n = 38,500) for sulfonylureas.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The overall mean age was 71.4 ± 10.9 years.

“The overall mean ± SD age was 71.4 ± 10.9 years”

The quote only partly states this claim.

Patients with cardiovascular disease had higher odds to start SGLT2i or GLP-1RA.

“Patients with cardiovascular disease or hyperlipidemia had higher odds to start SGLT2i or GLP-1RA.”

May combine two claims.

Asian patients were associated with lower odds of initiation of GLP-1RA but not SGLT2i.

“Hispanic and Asian patients were also associated with lower odds of initiation of GLP-1RA but not SGLT2i.”

May combine two claims.

There were significant differences in age, sex, race/ethnicity, socioeconomic groups, and clinical status between patients initiating SGLT2i or GLP-1RA and those initiating second-generation sulfonylureas.

“There were significant differences in age, sex, race/ethnicity racial/ethnical, socioeconomic groups, and clinical status of patients initiating SGLT2i and GLP-1RA, compared with second-generation sulfonylureas.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Sensitivity analysis findings were similar to the main analysis.

“The findings from the sensitivity analysis were similar to those from the main analysis (Table S7).”

May combine two claims.

Hispanic patients were associated with lower odds of initiation of GLP-1RA but not SGLT2i.

“Hispanic and Asian patients were also associated with lower odds of initiation of GLP-1RA but not SGLT2i.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A recent retrospective analysis using 2015-2019 Optum data suggested low SGLT2i prescription in commercially insured patients with type 2 diabetes and showed racial/ethnic, sex, and socioeconomic disparities in SGLT2i receipt versus other glucose-lowering medications.

“A recent retrospective analysis using 2015-2019 data from the Optum Clinformatics Data Mart suggested that the prescription of SGLT2i was low in commercially insured patients with type 2 diabetes and showed racial/ethnic, sex, and socioeconomic disparities in the receipt of SGLT2i therapy versus other glucose-lowering medications.18”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

There is potential for residual confounding with the use of retrospective data.

“There is potential for residual confounding with the use of retrospective data.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A sensitivity analysis was conducted excluding patients with CKD stages 4 and 5 and kidney failure because SGLT2i initiation was not recommended in advanced CKD during the study timeframe.

“We also conducted a sensitivity analysis to exclude patients with CKD stages 4 and 5 and kidney failure because the initiation of SGLT2i was not recommended in patients with advanced CKD stages and kidney failure during the study timeframe.”

May combine two claims.

Prescription of SGLT2i and GLP-1RA is low in both type 2 diabetes and patients with CKD.

“prescription of these newer glucose-lowering medications is low in both type 2 diabetes and patients with CKD.17,18”

• cites [17] Zhao J.Z. Weinhandl E.D. Carlson A.M. St. Peter W.L. Glucose-lowering medication use in CKD: analysis of US Medicare beneficiaries between 2007 and 2016 Kidney Med 3 2021 173 182.e1 10.1016/j.xkme.2020.09.016 33851113 PMC8039422 sourceNot checked — no full text of the source
• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

CKD and type 2 diabetes diagnosis, CKD stage, and patient clinical status were identified with diagnosis or procedure codes.

“CKD and type 2 diabetes diagnosis; CKD stage; and patient clinical status were identified with diagnosis or procedure codes.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Some patients in the Optum study may have had a relatively short baseline evaluation period, which could introduce bias in terms of number or type of comorbid conditions.

“Further, Optum investigators evaluated comorbid conditions from the earliest date of available data to the date of cohort entry. Some patients may have had a relatively short baseline evaluation period, which could introduce bias in terms of number or type of comorbid conditions.”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The subgroup analysis reported factors associated with SGLT2i use among patients with CKD and found that Black patients and female patients were associated with lower rates of adoption of SGLT2i; patients with metformin and insulin use were associated with high rates.

“The subgroup analysis reported factors associated with SGLT2i use among patients with CKD and found, similar to our study, that Black patients and female patients were associated with lower rates of adoption of SGLT2i; patients with metformin and insulin use were associated with high rates.”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The significant benefit of dapagliflozin on primary kidney outcomes was also shown in the Black subgroup.

“The significant benefit of dapagliflozin on primary kidney outcomes was also shown in the Black subgroup.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study reported that higher median household income (≥$100,000 vs <$50,000) was associated with a higher rate of adoption of SGLT2i.

“The study reported that higher median household income (≥$100,000 vs <$50, 000) was associated with a higher rate of adoption of SGLT2i.”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

The observed disparities represent a health disparity and a pharmacoequity issue that needs to be addressed to slow kidney disease progression in a population at higher risk of progressing to kidney failure.

“This represents a health disparity and a pharmacoequity issue that needs to be addressed to slow kidney disease progression in a population that is at higher risk of progressing to kidney failure.”

• AssumptionRests on an assumption: Sulfonylureas have not shown cardiovascular or kidney benefits and are more likely to cause hypoglycemia.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

They also showed that SGLT2i users were younger, and SGLT2i were prescribed less frequently to women than men and Black versus White patients.

“They also showed that SGLT2i users were younger, and SGLT2i were prescribed less frequently to women than men and Black versus White patients.”

• cites [24] McCoy R.G. Dykhoff H.J. Sangaralingham L. Adoption of new glucose-lowering medications in the U.S. - the case of SGLT2 inhibitors: nationwide cohort study Diabetes Technol Ther 21 2019 702 712 10.1089/dia.2019.0213 31418588 PMC7207017 sourceNot checked — no full text of the source

May combine two claims.

Two recent studies analyzed the use of SGLT2i based on sociodemographic and clinical factors, but both focused on commercially insured and Medicare Advantage patients without CKD.

“Two recent studies analyzed the use of SGLT2i based on sociodemographic and clinical factors. Both studies, however, focused on commercially insured and Medicare Advantage patients without CKD.”

• cites [18] Eberly L.A. Yang L. Eneanya N.D. Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US JAMA Netw Open 4 2021 e216139 10.1001/jamanetworkopen.2021.6139 PMC8050743 33856475 sourceNot checked — no full text of the source
• cites [24] McCoy R.G. Dykhoff H.J. Sangaralingham L. Adoption of new glucose-lowering medications in the U.S. - the case of SGLT2 inhibitors: nationwide cohort study Diabetes Technol Ther 21 2019 702 712 10.1089/dia.2019.0213 31418588 PMC7207017 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Zip code-level household median income was used to approximate personal income level, which is not included in Medicare claims data.

“Finally, zip code–level household median income was used to approximate personal income level, which is not included in Medicare claims data.”

Classified as probably not a substantial claim.

The Medicare data set does not include patients aged younger than 65 years, except for people with disabilities.

“The Medicare data set does not include patients aged younger than 65 years, except for people with disabilities.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Usage patterns may differ for patients enrolled in non-Part D prescription plans, Medicare Advantage plans, or other types of health insurance.

“Our analysis cohort consisted of patients with CKD enrolled in Medicare Part D coverage; thus, usage patterns may differ for patients enrolled in the non-Part D prescription plans, Medicare Advantage plans, or other types of health insurance.”

May combine two claims.

Approximately 49% of the CKD stage codes were CKD stage unknown or unspecified in the study cohort; thus, findings applied to patients with specific CKD stages known or determined.

“Approximately 49% of the CKD stage codes were CKD stage unknown or unspecified in our study cohort; thus, our findings applied to patients with specific CKD stages known or determined.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Clinical characteristics were measured based on administrative claims.

“Clinical characteristics were measured based on administrative claims.”

Classified as probably not a substantial claim.

The Medicare claims database provides comprehensive information on patient demographic characteristics, inpatient and outpatient diagnoses and procedures, and prescriptions.

“It provides comprehensive information on patient demographic characteristics, inpatient and outpatient diagnoses and procedures, and prescriptions.”

Classified as probably not a substantial claim.

The Medicare claims database is large enough to create a population for >53,000 patients meeting study criteria.

“The Medicare claims database is large enough to create a population for >53,000 patients meeting study criteria.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study only assessed the first prescription filled by new users after the diagnosis index date.

“The study only assessed the first prescription filled by new users after the diagnosis index date.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Medicare Part D beneficiaries may have chosen to use drug discount cards or coupons in lieu of their Medicare Part D prescription benefits, and we could not capture that information.

“In addition, Medicare Part D beneficiaries may have chosen to use drug discount cards or coupons in lieu of their Medicare Part D prescription benefits, and we could not capture that information.”