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BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks’ duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD − 0.55%, 95% CI − 0.62, − 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07227-0.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception–July 2019) for randomized controlled trials ≥ 52 weeks’ duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80–0.90), macrovascular complications (including stroke, RR 0.86, 0.78–0.95), and mortality (RR 0.89, 0.84–0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07105-9.

Background: Clinical trials of SGLT2Is and GLP1RAs have shown improved outcomes in patients with type 2 diabetes, but comprehensive data of their effectiveness in the Asian subpopulation are lacking. A systematic review and meta-analysis of clinical trials evaluating SGLT2Is and GLP1RAs was conducted to assess their efficacy in Asians with type 2 diabetes. Methods: PubMed, Scopus, and clinicaltrials.gov were searched from inception to July 2019 for randomized controlled trials (≥52 weeks) that enrolled Asians with type 2 diabetes and reported outcome data for SGLT2Is or GLP1RAs compared to placebo or other diabetic medications. Using random effect models, binary outcomes were evaluated with relative risks (RR) and continuous outcomes were evaluated with standardized mean differences (MD). Results: The analysis included 9 trials for SGLT2Is and 11 trials for GLP1RAs. Compared to placebo, SGLT2Is reduced HbA1c (MD: -0.70%, 95% CI: -1.29% to -0.10%) and weight (MD: -1.52 kg, -2.08 to -0.96 kg); compared to other diabetic medications, SGLT2Is reduced systolic blood pressure (MD: -6.42 mmHg, -9.43 to -3.41 mmHg). Compared to placebo, SGLT2Is increased the risk of genital infection (RR: 2.51, 1.01 to 6.21) but reduced the risk for renal events (RR: 0.69, 0.57 to 0.84). GLP1RAs were associated with lower HbA1c (MD: -0.65%, -1.07% to -0.22%) and weight (MD: -2.06 kg, -3.20 to -0.93 kg) when compared to other diabetic medications. GLP1RAs also reduced major cardiovascular events compared to placebo (RR: 0.72, 0.59 to 0.89). Data were not available for comparisons between GLP1RAs and placebo for other outcomes. Neither SGLT2Is or GLP1RAs had sufficient evidence to suggest their use was associated with a change in all-cause mortality. Conclusion: In the Asian subpopulation, clinical trials provide evidence for a reduction in cardiovascular risk factors and some diabetes-related adverse events by SGLT2Is and GLP1RAs. Disclosure R. Johnson: None. M. Franco: None. E. M. Staab: None. A. C. Knitter: None. W. Wan: None. J. Alexander: None. N. Laiteerapong: Other Relationship; Self; American Diabetes Association. Funding American Diabetes Association (1-18-JDF-037 to N.L.)

Background: Adults with type 2 diabetes and Medicaid insurance are a highly vulnerable population. Despite the vital role of primary care for diabetes management, few studies have examined how the type of primary care setting affects quality of care for this population, and existing studies have not examined data across the US. Since federally qualified health centers (FQHCs) are the primary care safety net for many Medicaid patients, we compared process of care outcomes and acute care utilization for non-elderly adult Medicaid enrollees with type 2 diabetes at FQHC vs. non-FQHC primary care settings. Methods: We analyzed 2012 Medicaid fee-for-service and managed care claims data in all 50 states and DC in order to compare 8 processes of care and acute care utilization for patients receiving care at FQHCs (N=121,977) vs. non-FQHCs (N=700,401). We used propensity score overlap weighting to obtain groups balanced on covariates, then used generalized estimating equation models to compare the two groups. Results: FQHC patients had 2.6-3.6% lower rates of each measure compared to non-FQHC patients, with the exception of a higher rate of diabetes education (relative risk, 1.09 [95% CI, 1.03-1.16]). Compared to non-FQHC patients, FQHC patients had more overall (incident rate ratio, 1.06 [1.05-1.07]) and diabetes-related emergency department (ED) visits (1.10 [1.08-1.13]), but fewer overall (0.87 [0.86-0.88]) and diabetes-related hospitalizations (0.79 [0.77-0.81]). Conclusions: Our findings suggest that Medicaid enrollees with type 2 diabetes receiving primary care at FQHCs may have limited access to both preventative and urgent diabetes care. FQHC patients with diabetes may visit EDs more frequently as a result of limited appointment availability or access to specialists at FQHCs. These results underscore the need for increased support and funding for Medicaid patients with type 2 diabetes, especially in FQHCs. Disclosure A. C. Knitter: None. M. Murugesan: None. L. Saulsberry: None. W. Wan: None. R. Nocon: None. E. Huang: None. J. Bolton: None. M. Chin: Advisory Panel; Self; Bristol-Myers Squibb Company. N. Laiteerapong: Other Relationship; Self; American Diabetes Association. Funding Health Resources and Services Administration (HHSH250201300025I); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK092949)

Background: Several large randomized trials suggest GLP-1RAs may reduce mortality in addition to lowering A1c in patients with T2D. Treatment algorithms from the ADA/EASD now recommend a GLP-1RA be initiated in patients with T2D who either have or are at high risk of atherosclerotic cardiovascular (CV) disease, regardless of A1c level. To better quantify the efficacy and safety of GLP-1RAs, we conducted a systematic review and meta-analysis of all randomized trials of this drug class. Methods: We searched PubMed and Scopus (inception to June 2019) for randomized trials of at least 52 weeks duration enrolling adults with T2D that compared GLP-1RAs with placebo. Outcomes included microvascular/macrovascular complications, mortality, change in cardiovascular risk factors, and adverse events. Continuous outcomes were calculated with standardized mean differences, and binary outcomes were calculated using odds ratios. Pooled analyses were performed with fixed and random effects models. Heterogeneity was assessed using the I2 statistic. Results: See Table for results. Conclusions: Patients with T2D who received GLP-1RAs when compared to placebo had a significantly lower rate of major adverse CV events and A1c. These findings support the current ADA/EASD treatment recommendations. Subsequent cost effectiveness analyses will help further inform healthcare policy decisions. Disclosure J. Alexander: None. E.M. Staab: None. W. Wan: None. M. Franco: None. A.C. Knitter: None. C.C. Thomas: None. V.G. Press: Consultant; Self; Humana, Vizient Inc. M. Zeytinoglu: None. R. Skandari: None. K.E. Gunter: None. B. Bindon: None. S. Jumani: None. S.D. Bolen: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. E. Huang: None. L.H. Philipson: None. N. Laiteerapong: None. Funding American Diabetes Association (1-18-JDF-037 to N.L.); National Institutes of Health (P30DK092949)

Background: Several large randomized trials suggest SGLT2Is may reduce mortality in addition to lowering A1c in patients with T2D. Treatment algorithms from the ADA and EASD now recommend a SGLT2I be initiated in patients with T2D who have chronic kidney disease or heart failure, regardless of A1c level. To better quantify the efficacy and safety of SGLT2Is, we conducted a systematic review and meta-analysis of all randomized trials of this drug class. Methods: We searched PubMed and Scopus (inception to June 2019) for randomized trials of at least 52 weeks duration enrolling adults with T2D that compared SGLT2Is with placebo. Outcomes included microvascular/macrovascular complications, mortality, change in cardiovascular (CV) risk factors, and adverse events. Continuous outcomes were calculated with standardized mean differences, and binary outcomes were calculated using odds ratios. Pooled analyses were performed with fixed and random effects models. Heterogeneity was assessed with the I2 statistic. Results: See Table for results. Conclusions: Patients who received SGLT2Is when compared to placebo had significantly lower rates of heart failure and A1c. These findings support the current ADA/EASD treatment recommendations. Subsequent cost effectiveness analyses will help further inform healthcare policy decisions. Disclosure J. Alexander: None. E.M. Staab: None. W. Wan: None. M. Franco: None. A.C. Knitter: None. C.C. Thomas: None. V.G. Press: Consultant; Self; Humana, Vizient Inc. M. Zeytinoglu: None. R. Skandari: None. K.E. Gunter: None. B. Bindon: None. S. Jumani: None. S.D. Bolen: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. E. Huang: None. L.H. Philipson: None. N. Laiteerapong: None. Funding American Diabetes Association (1-18-JDF-037 to N.L.); National Institutes of Health (P30DK092949)

Objective: We examined how diabetes medication initiation after first diagnosis varied by race/ethnicity. Method: We conducted a retrospective cohort study of 66,939 patients with newly diagnosed diabetes using data from a large integrated healthcare system. We classified patients into 12 race/ethnicity groups (see Table) and assessed their associations with diabetes medication initiation within 1, 12 and 18 months after diagnosis. We used a modified Poisson regression to estimate risk ratios adjusted for pre-diagnosis demographics and clinical characteristics. Results: Medications were started in 30%, 43% and 48% of patients within 1, 12 and 18 months, respectively. Within 1 month of diagnosis, Chinese, Filipino, and Native Hawaiian/Pacific islander were less likely to initiate a medication compared to whites. Results were consistent at 12 and 18 months, except that Japanese and blacks/African Americans were less likely to initiate compared to whites and that there was no difference between Native Hawaiian/Pacific islanders and whites at 18 months. Conclusions: We observed persistent racial differences between patients receiving any medication following initial diabetes diagnosis, with the largest differences for several Asian populations. Disclosure A.N. Winn: None. A.J. Karter: Research Support; Self; Dexcom, Inc. E.M. Staab: None. J. Liu: None. W. Wan: None. R. Skandari: None. A.C. Knitter: None. H.H. Moffet: None. D.R. Miller: None. M.E. Peek: Research Support; Self; Merck Foundation. E. Huang: None. N. Laiteerapong: None.