Several transitions, or new patterns and dynamics in the contributors and health outcomes, have altered the character and burden of the multi-decade, worldwide growth in prevalence of type 2 diabetes (T2DM). These changes have led to different needs for prevention and care. These dynamics have been driven by diverse demographic, socio-economic, behavioural, and health system response factors. In this Perspective, we describe these transitions and how their attributes have set the stage for multimorbidity, or multiple long-term conditions (MLTCs), to be the next major challenge in the diabetes epidemic. We also describe how the timing and character of these stages differ in high-, middle-, and low-income countries. These challenges call for innovation and a stronger focus on MLTCs across the spectrum of cause, effectiveness, and implementation studies to guide prevention and treatment priorities.