Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review.

The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide's adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide's safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis.

Adherence to GLP1-RA and SGLT2-I affects clinical outcomes and costs in patients with type 2 diabetes.

AIMS: To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007-2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system. RESULTS: After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72-0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55-0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA. CONCLUSIONS: Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.

Geographic variation and racial disparities in adoption of newer glucose-lowering drugs with cardiovascular benefits among US Medicare beneficiaries with type 2 diabetes.

BACKGROUND: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications. METHODS: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR. RESULTS: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%. CONCLUSIONS: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs.

Medicare formulary restrictions for glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors used in type 2 diabetes mellitus: 2019-2023.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) and sodium glucose cotransporter 2 inhibitors (SGLT2is) have proven benefits in patients with type 2 diabetes mellitus related to decreasing cardiovascular events and heart failure hospitalizations as well as preventing the progression of kidney disease. This led the American Diabetes Association (ADA) to update their guidelines in 2022 to recommend GLP1-RAs and SGLT2is as potential first-line options in patients with cardiorenal conditions. Formulary restrictions, such as step therapy and prior authorizations, can limit access to these beneficial medications. OBJECTIVE: To evaluate trends in Medicare formulary restrictions of GLP1-RAs and SGLT2is following the recommendations by the ADA for first-line use. METHODS: We conducted a retrospective cohort study of Quarter 1 Medicare formulary restrictions on GLP1-RAs and SGLT2is from 2019 to 2023. We analyzed changes in formulary restrictions by year, before and after the ADA first-line recommendations, single vs combination products, and products with and without other indications on a medication level (ie, each unique National Drug Code number on each unique formulary) and formulary level (ie, any prior authorization or step therapy requirements yield formulary restriction). RESULTS: We analyzed 12,212 unique Medicare formularies. GLP1-RAs were 12.5% less likely (relative risk [RR] = 0.87; 95% CI = 0.84-0.91; P < 0.001) and 33.2% less likely (RR = 0.67; 95% CI = 0.60-0.74; P < 0.001) to have restrictions after the ADA guideline changes on a medication and formulary level, respectively. SGLT2is were 87.8% less likely (RR = 0.12; 95% CI = 0.11-0.13; P < 0.001) and 53.0% less likely (RR = 0.47; 95% CI = 0.27-0.80; P = 0.005) to have restrictions after the ADA guideline changes on medication and formulary levels, respectively. CONCLUSIONS: Decreasing trends of medications and formularies with restrictions may indicate payers are recognizing GLP1-RAs and SGLT2is as potential first-line agents, aligning with ADA recommendations.

More questions than answers.

Weight loss and obesity have been challenging topics in science and public health for decades. While scientists have pursued understanding through studies of metabolism and the microbiome, public health scholars have shown that social factors such as poverty and inadequate health care are also major contributors. And though it is true that excess weight carries with it numerous comorbidities that lower life expectancy and add costs to the health care system, studies also show that it is possible to be overweight and healthy. That doesn't change the fact that obesity can be associated with poor mental health, in part because of the corrosive societal stigma that associates being overweight with mental weakness, not biochemistry.

Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model.

Objective: To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI). Methods: To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China's per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI. Results: During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD -1,418), lixisenatide (USD -1,713), semaglutide (USD -4,298), and liraglutide (USD -4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05). Conclusion: Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate.

Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes.

OBJECTIVE: To evaluate the comparative cardiovascular effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) in older adults with type 2 diabetes (T2D) across different frailty strata. RESEARCH DESIGN AND METHODS: We performed three 1:1 propensity score-matched cohort studies, each stratified by three frailty strata, using data from Medicare beneficiaries (2013-2019) with T2D who initiated SGLT-2is, GLP-1RAs, or DPP-4is. In time-to-event analyses, we assessed the primary cardiovascular effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, and all-cause mortality. The primary safety outcome was a composite of severe adverse events that have been linked to SGLT-2i or GLP-1RA use. RESULTS: Compared with DPP-4is, the overall hazard ratio (HR) for the primary effectiveness outcome associated with SGLT-2is (n = 120,202 matched pairs) was 0.72 (95% CI 0.69-0.75), corresponding to an incidence rate difference (IRD) of -13.35 (95% CI -15.06 to -11.64). IRD ranged from -6.74 (95% CI -8.61 to -4.87) in nonfrail to -27.24 (95% CI -41.64 to -12.84) in frail people (P for interaction < 0.01). Consistent benefits were observed for GLP-1RAs compared with DPP-4is (n = 113,864), with an overall HR of 0.74 (95% CI 0.71-0.77) and an IRD of -15.49 (95% CI -17.46 to -13.52). IRD in the lowest frailty stratum was -7.02 (95% CI -9.23 to -4.81) and -25.88 (95% CI -38.30 to -13.46) in the highest (P for interaction < 0.01). Results for SGLT-2is versus GLP-1RAs (n = 89,865) were comparable. Severe adverse events were not more frequent with SGLT-2is or GLP-1RAs than DPP-4is. CONCLUSIONS: SGLT-2is and GLP-1RAs safely improved cardiovascular outcomes and all-cause mortality, with the largest absolute benefits among frail people.

Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists.

Importance: Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive. Objective: To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity. Evidence Review: The annual US Food and Drug Administration's (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity. Findings: On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval. Conclusions and Relevance: Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.

Cost-Effectiveness of Newer Antidiabetic Drugs as Second-Line Treatment for Type 2 Diabetes: A Systematic Review.

INTRODUCTION: Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2 diabetes (T2D). This systematic review aimed to compare the cost-effectiveness of newer antidiabetic drugs specified as sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), and dipeptidyl peptidase 4 inhibitor (DPP-4i) for T2D in a second-line setting. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and all relevant published studies were searched comprehensively in electronic databases, including PubMed, Embase, Web of Science, and International Health Technology Assessment database published from April 2023. The quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 reporting checklists. RESULTS: We included 28 studies that met the inclusion criteria. Overall reporting of the identified studies largely met CHEERS 2022 recommendations. The CORE and Cardiff models were the most frequently utilized for pharmacoeconomic evaluation in T2D. Four studies consistently discovered that SGLT2i was more cost-effective than GLP-1RA in T2D who were not adequately controlled by metformin monotherapy. Four studies compared GLP-1RA with DPP-4i, sufonylurea (SU), or insulin. Except for one that demonstrated SU was cost-effective, all were GLP-1RA. Five studies revealed that SGLT2i was more cost-effective than DPP-4i or SU. Eleven studies indicated that DPP-4i was more cost-effective than traditional antidiabetic drugs. Four additional studies explored the cost-effectiveness of various antidiabetic drugs as second-line options, indicating that SU, SGLT2i, or meglitinides were more economically advantageous. The most common driven factors were the cost of new antidiabetic drugs. CONCLUSION: Newer antidiabetic drugs as second line are the cost-effective option for T2D from the cost-effectiveness perspective, especially SGLT2i.

Association of Prescription Co-payment With Adherence to Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Therapies in Patients With Heart Failure and Diabetes.

Importance: Type 2 diabetes (T2D) and heart failure (HF) prevalence are rising in the US. Although glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes for these conditions, high out-of-pocket costs may be associated with reduced medication adherence. Objective: To compare 1-year adherence to GLP1-RA and SGLT2i therapies by prescription co-payment level in individuals with T2D and/or HF. Design, Setting, and Participants: This retrospective cohort study used deidentified data from Optum Insight's Clinformatics Data Mart Database of enrollees with commercial and Medicare health insurance plans. Individuals aged 18 years or older with T2D and/or HF who had a prescription claim for a GLP1-RA or SLGT2i from January 1, 2014, to September 30, 2020, were included. Exposures: Prescription co-payment, categorized as low (<$10), medium ($10 to<$50), and high (≥$50). Main Outcomes and Measures: The primary outcome was medication adherence, defined as a proportion of days covered (PDC) of 80% or greater at 1 year. Logistic regression models were used to examine the association between co-payment and adherence, adjusting for patient demographics, medical comorbidities, and socioeconomic factors. Results: A total of 94 610 individuals (mean [SD] age, 61.8 [11.4] years; 51 226 [54.1%] male) were prescribed GLP1-RA or SGLT2i therapy. Overall, 39 149 individuals had a claim for a GLP1-RA, of whom 25 557 (65.3%) had a PDC of 80% or greater at 1 year. In fully adjusted models, individuals with a medium (adjusted odds ratio [AOR], 0.62; 95% CI, 0.58-0.67) or high (AOR, 0.47; 95% CI, 0.44-0.51) co-payment were less likely to have a PDC of 80% or greater with a GLP1-RA compared with those with a low co-payment. Overall, 51 072 individuals had a claim for an SGLT2i, of whom 37 339 (73.1%) had a PDC of 80% or greater at 1 year. Individuals with a medium (AOR, 0.67; 95% CI, 0.63-0.72) or high (AOR, 0.68; 95% CI, 0.63-0.72) co-payment were less likely to have a PDC of 80% or greater with an SGLT2i compared with those with a low co-payment. Conclusions and Relevance: In this cohort study of individuals with T2D and/or HF, 1-year adherence to GLP1-RA or SGLT2i therapies was highest among individuals with a low co-payment. Improving adherence to guideline-based therapies may require interventions that reduce out-of-pocket prescription costs.

Primary Occurrence of Cardiovascular Events After Adding Sodium-Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes.

BACKGROUND: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease. OBJECTIVE: To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention. DESIGN: Retrospective cohort study of U.S. veterans from 2001 to 2019. SETTING: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. PATIENTS: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. MEASUREMENTS: Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates. RESULTS: The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium-glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [-1.12 to 3.32]) compared with DPP4i. LIMITATION: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. CONCLUSION: The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention. PRIMARY FUNDING SOURCE: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.

Persistence on Novel Cardioprotective Antihyperglycemic Therapies in the United States.

Selected glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have cardioprotective effects in patients with type 2 diabetes mellitus (T2D) and elevated cardiovascular risk. Prescription and consistent use of these medications are essential to realizing their benefits. In a nationwide deidentified United States administrative claims database of adults with T2D, the prescription practices of GLP-1RAs and SGLT-2i were evaluated across guideline-directed co-morbidity indications from 2018 to 2020. The monthly fill rates were assessed for 12 months after the initiation of therapy by calculating the proportion of days with consistent medication use. Of 587,657 subjects with T2D, 80,196 (13.6%) were prescribed GLP-1RAs and 68,149 (11.5%) SGLT-2i from 2018 to 2020, representing 12.9% and 11.6% of patients with indications for each medication, respectively. In new initiators, 1-year fill rate was 52.5% for GLP-1RAs and 52.9% for SGLT-2i, which was higher for patients with commercial insurance than those with Medicare Advantage plans for both GLP-1RAs (59.3% vs 51.0%, p <0.001) and SGLT-2i (63.4% vs 50.3%, p <0.001). After adjusting for co-morbidities, there were higher rates of prescription fills for patients with commercial insurance (odds ratio 1.17, 95% confidence interval 1.06 to 1.29 for GLP-1RAs, and 1.59 [1.42 to 1.77] for SGLT-2i); and higher income (odds ratio 1.09 [1.06 to 1.12] for GLP-1RAs, and 1.06 [1.03 to 1.1] for SGLT-2i). From 2018 to 2020, the use of GLP-1RAs and SGLT-2i remained limited to fewer than 1 in 8 patients with T2D and indications, with 1-year fill rates around 50%. The low and inconsistent use of these medications compromises their longitudinal health outcome benefits in a period of expanding indications for their use.

Value of GLP-1 receptor agonists versus long-acting insulins for type 2 diabetes patients with and without established cardiovascular or chronic kidney diseases: A model-based cost-effectiveness analysis using real-world data.

AIMS: To evaluate the cost-effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) in patients with type 2 diabetes (T2D) using real-world data. METHODS: A Markov model was utilized to estimate healthcare costs (US$) and quality-adjusted life-years (QALYs) of receiving treatments over 10 years from the healthcare sector perspective. Model inputs were derived from the analyses of Taiwan's National Health Insurance Research Database or published literature on Taiwanese T2D populations. Base-case analysis was performed for the overall study cohort and subgroup analyses were stratified by the presence or absence of established cardiovascular diseases (CVDs) or chronic kidney diseases (CKDs). RESULTS: Overall, using GLP-1RAs versus LAIs cost $6,053 per QALY gained. Results were robust across sensitivity and scenario analyses. Among patients with established CVDs and CKDs, GLP-1RA versus LAI therapy saved $673 (cost-saving) and cost $1,675 per QALY gained, respectively. Among patients without established CVDs and CKDs, GLP-1RA versus LAI therapy cost $9,093 and $7,659 per QALY gained, respectively. CONCLUSIONS: Using GLP-1RAs versus LAIs for T2D patients represented good economic value in real-world practice. Pronounced economic benefits of GLP-1RA therapy among those with prior CVDs or CKDs support rational treatment decisions and optimal healthcare resource allocation for these patients.

Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.

AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes.

The clinical evidence base for evaluating modern type 2 diabetes interventions has expanded greatly in recent years, with numerous efficacious treatment options available (including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors). The cardiovascular safety of these interventions has been assessed individually versus placebo in numerous cardiovascular outcomes trials (CVOTs), statistically powered to detect differences in a composite endpoint of major adverse cardiovascular events. There have been growing calls to incorporate these data in the long-term modelling of type 2 diabetes interventions because current diabetes models were developed prior to the conduct of the CVOTs and therefore rely on risk equations developed in the absence of these data. However, there are numerous challenges and pitfalls to avoid when using data from CVOTs. The primary concerns are around the heterogeneity of the trials, which have different study durations, inclusion criteria, rescue medication protocols and endpoint definitions; this results in significant uncertainty when comparing two or more interventions evaluated in separate CVOTs, as robust adjustment for these differences is difficult. Analyses using CVOT data inappropriately can dilute clear evidence from head-to-head clinical trials, and blur healthcare decision making. Calibration of existing models may represent an approach to incorporating CVOT data into diabetes modelling, but this can only offer a valid comparison of one intervention versus placebo based on a single CVOT. Ideally, model development should utilize patient-level data from CVOTs to prepare novel risk equations that can better model modern therapies for type 2 diabetes.

Real-world national trends and socio-economic factors preference of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in China.

Backgrounds: Robust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China. Method: A total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics. Results: Annual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency. Conclusions: SGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.

Association of Race and Ethnicity With Prescription of SGLT2 Inhibitors and GLP1 Receptor Agonists Among Patients With Type 2 Diabetes in the Veterans Health Administration System.

Importance: Novel therapies for type 2 diabetes can reduce the risk of cardiovascular disease and chronic kidney disease progression. The equitability of these agents' prescription across racial and ethnic groups has not been well-evaluated. Objective: To investigate differences in the prescription of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) among adult patients with type 2 diabetes by racial and ethnic groups. Design, Setting, and Participants: Cross-sectional analysis of data from the US Veterans Health Administration's Corporate Data Warehouse. The sample included adult patients with type 2 diabetes and at least 2 primary care clinic visits from January 1, 2019, to December 31, 2020. Exposures: Self-identified race and self-identified ethnicity. Main Outcomes and Measures: The primary outcomes were prevalent SGLT2i or GLP-1 RA prescription, defined as any active prescription during the study period. Results: Among 1 197 914 patients (mean age, 68 years; 96% men; 1% American Indian or Alaska Native, 2% Asian, Native Hawaiian, or Other Pacific Islander, 20% Black or African American, 71% White, and 7% of Hispanic or Latino ethnicity), 10.7% and 7.7% were prescribed an SGLT2i or a GLP-1 RA, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 8.4% among American Indian or Alaska Native patients; 11.8% and 8% among Asian, Native Hawaiian, or Other Pacific Islander patients; 8.8% and 6.1% among Black or African American patients; and 11.3% and 8.2% among White patients, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 7.1% among Hispanic or Latino patients and 10.7% and 7.8% among non-Hispanic or Latino patients. After accounting for patient- and system-level factors, all racial groups had significantly lower odds of SGLT2i and GLP-1 RA prescription compared with White patients. Black patients had the lowest odds of prescription compared with White patients (adjusted odds ratio, 0.72 [95% CI, 0.71-0.74] for SGLT2i and 0.64 [95% CI, 0.63-0.66] for GLP-1 RA). Patients of Hispanic or Latino ethnicity had significantly lower odds of prescription (0.90 [95% CI, 0.88-0.93] for SGLT2i and 0.88 [95% CI, 0.85-0.91] for GLP-1 RA) compared with non-Hispanic or Latino patients. Conclusions and Relevance: Among patients with type 2 diabetes in the Veterans Health Administration system during 2019 and 2020, prescription rates of SGLT2i and GLP-1 RA medications were low, and individuals of several different racial groups and those of Hispanic ethnicity had statistically significantly lower odds of receiving prescriptions for these medications compared with individuals of White race and non-Hispanic ethnicity. Further research is needed to understand the mechanisms underlying these differences in rates of prescribing and the potential relationship with differences in clinical outcomes.

Oral versus subcutaneous semaglutide for prevention of major adverse cardiovascular events: cost per outcome analysis of SUSTAIN-6 and PIONEER-6.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1a), reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over the subcutaneous form. Our objective was to compare the value for money of the two modalities by assessing the cost needed to treat (CNT) to prevent MACE. METHODS: The CNT to prevent MACE was figured by multiplying the one-year number needed to treat (NNT) with either oral or subcutaneous semaglutide by the annual cost of therapy. Efficacy estimates and the resulting NNT figures were extracted from the published results of the SUSTAIN-6 and the PIONEER-6 trials for the injectable and oral versions of semaglutide, respectively. Drug costs were estimated as 75% of the United States national average drug acquisition cost listing in June 2021. We performed a scenario analysis to mitigate the primary differences between the populations in the two trials. Sensitivity analysis was performed to evaluate the effect of price changes of the interventions. RESULTS: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 was $966,693 ($594,888-$5,035,302) compared to $948,689 ($463,465-∞) with oral semaglutide in PIONEER-6. The scenario analysis demonstrated a 17% lower CNT for oral semaglutide. The difference between CNTs was sensitive to price fluctuations of the two interventions. CONCLUSIONS: Oral and subcutaneous semaglutide prescribed to prevent MACE in patients with T2DM provide similar value for money. The choice between both therapies should be guided mainly by patient preferences.