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• Studies using strict definitions to investigate the association between metabolic phenotypes (MP) and diabetes are scarce. • Participants with obesity/healthy MP were not at increased diabetes risk compared to the ones with normal weight/healthy MP. • Reduced grip strength was associated with a higher risk of diabetes incidence in the long-term. • High grip strength attenuated the risk associated with metabolically unhealthy phenotypes. The association of diabetes risk in the long-term, metabolic phenotypes (MP) and muscle strength is unclear. We aimed to investigate the association between strictly defined MP, grip strength (GS) and diabetes. MP were defined according to BMI and presence of any individual metabolic abnormality for ≥18 years, in participants of the North West Adelaide Health Study (Australia) free of diabetes at baseline. The association of MP and dominant hand GS with incident diabetes over 15-years follow-up and the moderation effect of GS on the association between diabetes and MP were investigated by logistic regression models. Of 3039 participants followed over 13.3 years (SD 2.6), 236 (7.8%) developed diabetes. Compared to the metabolically healthy (MH) normal weight phenotype, the metabolically unhealthy (MU) overweight (OR 6.15, 95%CI 2.43–15.59) and obese (OR 12.32, 95%CI 4.97–30.52) phenotypes were associated with a high risk of diabetes, but not the MU normal weight (OR 1.73, 95%CI 0.57–5.25), MH overweight (OR 1.15, 95%CI 0.31–4.31) or MH obese phenotypes (OR 0.77, 0.07–8.89). GS was inversely associated with diabetes (OR 0.97, 95% CI 0.95–0.99) and attenuated the risk associated with MU overweight (beta = −0.296, p = 0.039) and MU normal weight (beta = −0.773; p for interaction = 0.009). Strictly defined MP (rather than based on metabolic syndrome criteria) and GS, a proxy of muscle strength, might be useful for stratifying the risk of diabetes in the long-term. Improving muscle strength might be an important strategy to reduce diabetes risk. [ABSTRACT FROM AUTHOR]