Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings: In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding: Bill & Melinda Gates Foundation. © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseDepartment of Biotechnology, Ministry of Science and Technology, India, DBT; KACSAT; Ministry of Business and Knowledge, (2020 BP 00261); Health and Nutrition, (175042); King Abdulaziz University, KAU; International Center of Medical Sciences Research, (44000); University of Sydney, USYD; University Hospital Essen; National Heart Foundation of Australia, (102597); Korea Institute for Advancement of Technology, KIAT; Fundação de Amparo à Pesquisa do Estado de Minas Gerais, FAPEMIG; Science and Technology Development Fund, STDF; California Department of Fish and Game, DFG, (FU 356/12-2); Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq; Marga und Walter Boll-Stiftung; Fonds de recherche du Québec - Santé, China Scholarship Council; Ministry of Education, MOE; Academy of Finland, AKA, (350426); Den Sociale Fond; International Medical University, IMU; Ateneo de Manila University; Bundesministerium für Bildung und Forschung, BMBF, (01EA1808A); Ministero della Salute, (34/2017); McGill University, MGU; The Wellcome Trust DBT India Alliance, WTDBT India Alliance, (IA/CPHE/17/1/503345); Public Health Agency of Canada, PHAC; Australian Government Research Training Program; Social Science Foundation of Jiangsu Province, (21GLD008); National Institute of Biomedical Innovation, NIBIO; National Heart, Lung, and Blood Institute, NHLBI, (K23HL157766, CENTRO-04-3559-FSE-000162); University of Aberdeen, ABDN; Department of Sport and Recreation, Government of Western Australia, DSR; RTP; Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq; Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, (304224/2022-7); Academy of Scientific Research and Technology, ASRT; Australian Research Council, ARC, (FT220100857); Applied Molecular Biosciences Unit, UCIBIO, (LA/P/0140/2020); European Commission, EC; King Abdulaziz City for Science and Technology, KACST; Anima Institute; Horizon 2020 Framework Programme, H2020, (EDCTP-RIA2016E-1609); Fundação de Amparo à Pesquisa do Estado de Minas Gerais, FAPEMIG; Fundação para a Ciência e a Tecnologia, FCT, (UIDB/04084/2020); Pan African Network for Rapid Research; Department of Environmental Health Engineering of Isfahan University of Medical Sciences; National Natural Science Foundation of China, NSFC, (72204112); Universidad de La Sabana; Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq; National Institute on Aging, NIA, (R01AG062553); Central University of Kerala, CUK; Taibah University; Jazan University; Wellcome Trust, WT, (R024227, 221854/Z/20/Z); Chandigarh University, CU; Fuel Cell Technologies Program, FCT, (UIDB/04378/2020, UIDP/04378/2020); Mecanismo para la Recuperación y la Resiliencia; Fundação para a Ciência e a Tecnologia, FCT; National Health and Medical Research Council, NHMRC; US-Egypt Science & Technology joint Fund; National Science and Technology Council, NSTC, (NSTC 111-2410-H-003-100-SSS); Deutsche Forschungsgemeinschaft, DFG; Instituto de Salud Carlos III, ISCIII, (RD21/0005/0001); Office of the Secretary of Transportation, OST; Università ta' Malta, UM; Preparedness for Infectious Diseases Epidemics Consortium; European and Developing Countries Clinical Trials Partnership, EDCTP; National Heart Foundation of Australia; Beatriu de Pinós; Manipal Academy of Higher Education, Manipal, India; Bill and Melinda Gates Foundation, BMGF; German National Cohort Study; Institute for Health Technology Assessment, (465518/2014-1); Medical Research Council, MRC; Nassau University Medical Centers and Cleveland Clinic Foundation; National Health and Medical Research Council, NHMRC; Scientific Employment Stimulus, (CEECIND/01768/2021); Department of Community Medicine, School of Medicine; Ministry of Higher Education, Malaysia, MOHE, (FRGS/1/2020/STG03/USM/03/5); Heart Foundation, THF; Centre of Studies in Geography and Spatial Planning; Manipal Academy of Higher Education, MAHE; MRR; JSS Academy of Higher Education and Research, JSS AHER; University Grants Commission, UGC; Institute of Applied Health Sciences; PANDORA-ID-NET; Universiti Kebangsaan Malaysia, UKM; Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja, MPNTR, (2011-2023); Taipei Medical University for Doctoral Education; Ministry of Trade, Industry and Energy, MOTIE, (P0017805); Ministry of Science, and Technological Development and Innovation of the Republic of Serbia, (451-03-47/2023-01/200111); China Medical University, Taiwan, CMU, (CMU111-MF-55); University of New South Wales, Australia; Department of Community Medicine, Kasturba Medical College; Belgian American Educational Foundation, BAEF; Competence Cluster for Nutrition and Cardiovascular Health; National Research Foundation of Korea, NRF, (NRF-2021R1I1A4A01057428); Deanship of Scientific Research at Shaqra University; Institute for Maternal and Child Health IRCCS Burlo Garofolo