Prediabetes reversal yields decades-long cardiovascular benefits

Remission of prediabetes has been found to substantially lower the risk of cardiovascular morbidity and mortality in a study, and this cardiovascular protection persists for decades.

The finding was based on a post hoc analysis of data from two landmark diabetes prevention trials—the US Diabetes Prevention Program Outcomes Study (DPPOS) and the Chinese DaQing Diabetes Prevention Outcomes Study (DaQingDPOS).

US population

In DPPOS, the event rate for the primary composite outcome of cardiovascular death or hospitalization for heart failure (HF) over a median follow-up of 20 years was significantly lower among participants who did vs did not achieve the American Diabetes Association (ADA)-defined remission at 1 year after intervention (1.74 vs 4.17 per 1,000 person-years; p=0.013). Prediabetes remission was associated with a 59-percent reduction in the risk of the primary composite outcome (adjusted hazard ratio [aHR], 0.41, 95 percent confidence interval [CI], 0.20–0.84; p=0.014). [Lancet 2026;14:137-148]

Participants who achieved remission also had lower rates of extended major adverse cardiovascular events (MACE) (6.23 vs 9.95 per 1,000 person-years; p=0.016) and mortality (6.05 vs 9.18 per 1,000 person-years; p=0.033) compared with those who did not achieve remission. The corresponding aHRs were 0.70 (95 percent CI, 0.47–1.04; p=0.078) and 0.78 (95 percent CI, 0.53–1.16; p=0.226).

Chinese population

The findings in DPPOS were replicated in the DaQingDPOS with a follow-up duration of more than 30 years.

Compared with those who did not achieve prediabetes remission, participants who did go into remission after a 6-year lifestyle intervention had lower event rates for cardiovascular death or hospitalization for HF (9.5 vs 17 per 1,000 person-years; aHR, 0.49, 95 percent CI, 0.28–0.84; p=0.010), hospitalization for HF (3.8 vs 7.9 per 1,000 person-years; aHR, 0.39, 95 percent CI, 0.16–0.93; p=0.034), cardiovascular death (8.2 vs 13.8 per 1,000 person-years; aHR, 0.56, 95 percent CI, 0.31–1.02; p=0.059), and MACE (27 vs 45.9 per 1,000 person-years; aHR, 0.61, 95 percent CI, 0.43–0.87; p=0.006).

Pooled meta-analysis of data from the DPPOS and DaQingDPOS cohorts confirmed the individual findings.

ADA-defined remission of prediabetes was associated with a 53-percent reduction in the risk of cardiovascular death or hospitalization for HF (pooled aHR, 0.47, 95 percent CI, 0.30–0.72; p=0.0006; I²=0.0 percent) and a 37-percent decrease in the risk of all-cause mortality (pooled aHR, 0.63, 95 percent CI, 0.47–0.84; p=0.0014; I²=62 percent).

Legacy effect

Taken together, the findings “indicate that prediabetes remission—reached after 1 year of intervention in DPPOS or after 6 years in DaQingDPOS—is associated with a legacy effect on cardiovascular outcomes persisting 2–3 decades after the intervention concluded,” said first study author Dr Elsa Vazquez Arreola from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Arizona, US.

These associations were consistent whether normal glucose regulation was defined by the ADA (FPG <100 mg/dL, 2-h plasma glucose <140 mg/dL, and HbA_1c <5.7 percent) or the WHO criteria (FPG 110–125 mg/dL and 2-h plasma glucose 140–199 mg/dL), among participants who went into remission at least once during follow-up, and despite adjustment for the development of type 2 diabetes, Arreola added.

She pointed out that weight loss alone does not explain the cardiovascular benefits observed following diabetes remission.

“Participants who reached remission and those who did not, following a multimodal lifestyle intervention, experienced comparable weight loss (>5 percent of initial bodyweight) and total body fat loss. However, remission was accompanied by greater improvements in insulin sensitivity, more pronounced reductions in visceral adipose tissue, and lower levels of low-grade inflammation,” Arreola explained.

“Thus, remission from prediabetes to normoglycaemia might serve as both a biomarker and a therapeutic target, encapsulating a spectrum of favourable cardiometabolic changes,” she said.

Prediabetes as a clinical aim

“Remission from prediabetes or type 2 diabetes has emerged as a tangible clinical aim, supported by evidence from intensive lifestyle interventions, metabolic surgery, and pharmacological studies demonstrating that a return to normoglycaemia improves health outcomes,” according to Lancet Diabetes & Endocrinology’s editorial. [Lancet 2026;14:93]

The editorial highlighted several challenges that prevent the integration of prediabetes remission into global health surveillance and clinical practice. These include the lack of standard definition for both prediabetes and remission, as well as the limited surveillance data in low- and middle-income countries where diabetes-related mortality is higher.

“Diabetes is a complex and highly heterogeneous disease. Only when diabetes epidemiology can capture the full spectrum can global diabetes policy be accurate, evidence-based, and truly impactful,” according to the editorial.

The DPPOS and DaQingDPOS cohorts consisted of 2,402 and 540 participants, respectively.

In DPPOS, 275 participants (mean age at baseline 46.9 years, mean BMI at baseline 32.3 kg/m²) reached remission after 1 year of an intensive lifestyle intervention program (reduce weight by 7 percent and increase physical activity time to 150 min per week), metformin treatment (850 mg twice a day as tolerated), or placebo.

In DaQingDPOS, 72 participants (mean age at baseline 43 years, 63.9 percent male, mean BMI at baseline 33 kg/m²) achieved remission after 6 years of intervention with diet modification, exercise, or diet plus exercise.