An estimated 537 million people were living with diabetes worldwide in 2021, and this number is expected to increase based on trends and future projections, suggesting that by 2045 the absolute number of people with diabetes will have increased by 46%. ¹ The global prevalence of diabetes is estimated to be over 10%, with the highest prevalence rate observed in low and middle-income countries, meaning that three out of four adults with diabetes live in these regions. ² In Colombia, the prevalence for type 2 diabetes mellitus (T2DM) ranges from 7.1%-8.5% overall, with wide variations between rural areas (1.4%-7.9%) and urban locations (1%-46%), representing the fifth leading cause of death with a rate of 15 deaths per 100,000 individuals. ³ This is a worrying finding, as the burden of diabetes is accompanied by large healthcare expenditures, accounting for 966 billion USD worldwide and 2.6 billion dollars annually in Colombia. ^{2 , 3}

Until recently, 12 classes of drugs were approved to treat T2DM, with a further option -the dual targeted tirzepatide-, receiving Food and Drug and Administration (FDA) approval in May 2022. ^{4 , 5} These treatments are either oral or injectable, aiming to prevent or delay the occurrence of microvascular and macrovascular complications, the main causes of morbidity and mortality in patients with diabetes. ⁵ Enhanced glycemic control can be achieved with glucagon-like peptide-1 (GLP-1) receptor agonists, recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) as a first-line treatment option for individuals with T2DM with or at high risk for cardiovascular disease, heart failure, and/or chronic kidney disease. Furthermore, in these patients a GLP-1 receptor agonist is recommended over insulin when possible, and it is also the preferred addition to basal insulin for combined injection therapy. ⁶

Multiple studies have shown robust evidence with this drug class for cardiovascular benefits among patients with T2DM. A systematic review with meta-analysis that included seven clinical trials showed that, overall, the GLP-1 receptor agonist family reduced major adverse cardiovascular events (MACE), including cardiovascular death, stroke, or myocardial infarction, by 12%. ⁷ Similar findings were also shown in another meta-analysis, demonstrating that GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke), and a 12% relative risk reduction in all-cause mortality. ⁸ Once-weekly semaglutide and dulaglutide are GLP-1 receptor agonists approved for the treatment of T2DM by the FDA, European Medicines Agency (EMA) and the Colombia National Food and Drug Surveillance Institute (INVIMA), ^{9 , 10} with demonstrated efficacy in the SUSTAIN clinical trial program for the former and the AWARD trial program for the latter. ^{11 , 12}

The purpose of our study was to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective, as has been recommended in multiple methodological guidelines for economic evaluations. ¹³

We conducted an evaluation of the short-term cost-effectiveness of the GLP-1 receptor agonists semaglutide and dulaglutide, with cost-effectiveness assessed through the development of a cost of control model, in order to evaluate the numbers needed to treat (NNT) as well as the absolute and relative costs of bringing a single patient to each of the pre-specified composite and single endpoints in the SUSTAIN 7 trial, which demonstrated a higher efficacy with semaglutide for all outcomes. ¹⁴

The calculations from our analysis suggest that achieving clinically relevant endpoints from SUSTAIN 7 would result in economic savings with once weekly semaglutide, compared to dulaglutide after one year of treatment. The annual drug cost for both medications was similar in the base case, with our results being consistent with previous studies that have also demonstrated that semaglutide is a cost-effective option when compared to dulaglutide. ^{18 – 22} In this study, we synthesized the effectiveness and expenditure evidence and found that semaglutide was associated with the lowest cost per patient reaching disease control for all endpoints, findings that were reaffirmed in our sensitivity analyses.

This study has important implications for stakeholders considering this is the first cost-effectiveness analysis to date comparing subcutaneous semaglutide and dulaglutide in the Colombian diabetic population, potentially allowing a better allocation of resources. Previous studies have demonstrated the superiority of semaglutide over dulaglutide in both short and long-term cost-effectiveness analyses, most of them being carried out in high-income countries. ^{18 – 22}

In Colombia, insurers (payers) are recognized as key players in the healthcare system. These payers have spent 30 years building their expertise in managing healthcare system resources and have had to adapt quickly to the inclusion of greater benefits, including the introduction of new medications, many of which are high-cost. ²³ This puts the short and long-term sustainability of health insurers in Colombia at risk. Payers in Colombia are gradually shifting towards a more detailed examination of the cost-effectiveness relationship of different health technologies. Due to operational issues, expertise, and human talent, these reviews have not yet been carried out in the long term. Additionally, due to operational considerations and variability in the insured population over time, there is currently no interest in conducting these analyses over long time horizons. In this line of thought, payers have an interest in short-term analysis and cost savings for the system. ^{24 , 25} We believe that using this cost-control economic study design provides a valuable tool for these types of participants in the Colombian healthcare system in the short term (1 year), enabling them to make decisions regarding the prioritization of medications and the access granted to each molecule.

This study has several limitations. First, we restricted our comparison to semaglutide versus dulaglutide. It is important to acknowledge that there are other available molecules in the Colombian market. Second, we limited the costs in the analysis to drugs, as they were expected to be the major drivers of the cost-effectiveness of semaglutide and dulaglutide. Therefore, this model did not account for all potential costs. Third, the analysis takes a third-payer perspective over a short-term horizon. Alternative perspectives and time horizons may result in variable cost-effectiveness estimations, and as such, additional cost-effectiveness studies for these molecules with longer time horizons would be a welcome complement for our study. Fourth, we included prices disregarding potential discounts or refunds, which payers might need to consider in their decision-making processes.

This is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide. Additional cost-effectiveness studies are war-ranted to evaluate the long-term cost-effectiveness of these molecules in the Colombian diabetic population.