This is observational follow-up of the Diabetes Prevention Program and its Outcomes Study. Between 1996 and 1999, 3,234 adults with prediabetes were randomly assigned at 27 US sites to an intensive lifestyle intervention, metformin, or placebo. Medicare morbidity data through 2021 were available for 1,173 of them who consented. Median age at the end was 74 (interquartile range 70 to 80), and 68 per cent were female. The outcome was multimorbidity, defined as at least two of 15 chronic conditions.
By the end of follow-up, 997 of 1,173 (85 per cent) had at least two conditions, with a median of five. The risk of multimorbidity was lower in the lifestyle group than placebo, hazard ratio 0.79 (95% CI 0.68 to 0.93). Metformin did not differ from placebo, hazard ratio 0.91 (0.78 to 1.07). The lifestyle finding held when diabetes itself was removed from the definition, so this is not simply a restatement of diabetes prevention. Restricted to pairs of the costliest conditions, the lifestyle hazard ratio was 0.57 (0.38 to 0.85).
What this changes is how you talk about prevention. A structured programme delivered in the late 1990s was still associated with fewer chronic conditions more than two decades later, at an age when almost everyone has accumulated several. The honest caveat is that this is observational follow-up of a randomised trial rather than a randomised comparison of this outcome, so it is association, not proof. Even so, it is the strongest long-horizon argument available for funding and referring to real lifestyle programmes, and against treating metformin as an equivalent, easier substitute.
- Refer to a structured lifestyle programme, not just verbal advice, for every patient with prediabetes.
- Do not offer metformin as an equal alternative when the conversation is about preventing chronic disease.
- Set the time horizon honestly - the separation here shows up in disease burden decades later, not in months.
- Audit how many of your prediabetes patients were actually referred, rather than simply told to lose weight.
- Keep metformin where it is indicated for glucose control; this analysis is about multimorbidity, not glycaemia.
The statistics, in plain English
A hazard ratio of 0.79 means that at any given moment the lifestyle group was about 21 per cent less likely to cross into multimorbidity than placebo, and because the confidence interval runs from 0.68 to 0.93 and stays below 1.0, the direction is reliable. For metformin the interval runs from 0.78 to 1.07 and includes 1.0, which means the data are compatible with a modest benefit, no effect, or a small harm - the honest reading is no demonstrated difference. The much lower figure for the costliest condition pairs, 0.57, is based on fewer events, which is why its interval is wider; treat it as supportive rather than as a separate finding.
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