ImportanceAge-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD.ObjectiveTo investigate the association between metformin use and age-related macular degeneration (AMD).Design, Setting, and ParticipantsThe Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022.InterventionsParticipants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo.Main Outcomes and MeasuresPrevalence of AMD in the treatment arms.ResultsOf 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02).Conclusions and RelevanceThese data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

OBJECTIVE To determine whether interventions that slow or prevent the development of type 2 diabetes in those at risk reduce the subsequent prevalence of diabetic retinopathy. RESEARCH DESIGN AND METHODS The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study grading system, with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates, or hemorrhage, or worse) in either eye. RESULTS Despite reduced progression to diabetes in the ILS and MET groups compared with PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11, or 16 years of follow-up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin, regardless of treatment group assignment. CONCLUSION Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.

IntroductionType 2 diabetes mellitus (T2DM) is associated with alterations in bone mineral density (BMD), but association between prediabetes and BMD is unclear.MethodsWe analyzed BMD among the initially normoglycemic participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study in relation to incident prediabetes during 5 years of follow-up.Results and DiscussionA total of 343 participants (193 Black, 150 White) underwent DEXA during Year 1 of POP-ABC and were followed quarterly for 5 years. The mean age was 44.2 ± 10.6 years; BMI was 30.2 ± 7.23 kg/m2. At baseline, the mean BMD was 1.176 ± 0.135 g/cm2 (1.230 ± 0.124 g/cm2 in men vs. 1.154 ± 0.134 g/cm2 in women, P<0.0001; 1.203 ± 0.114 g/cm2 in Black vs. 1.146 ± 0.150 g/cm2 in White participants, P=0.0003). During 5 years of follow-up, 101 participants developed prediabetes and 10 subjects developed T2DM (progressors); 232 were nonprogressors. Progressors to prediabetes had numerically higher baseline BMD and experienced lower 1-year decline in BMD (P<0.0001) compared with nonprogressors. From Kaplan-Meier analysis, the time to 50% prediabetes survival was 2.15 y among participants in the lowest quartile of baseline BMD, longer than those in higher quartiles (1.31 – 1.41 y). Values for BMD correlated inversely with age and adiponectin levels, and positively with BMI. In logistic regression analysis, BMD z score significantly predicted incident prediabetes: more negative BMD z scores were associated with decreased incident prediabetes (odds ratio 0.598 [95% confidence interval 0.407 - 0.877], P=0.0085), after controlling for age, BMI, change in BMI, ethnicity, blood glucose and adiponectin.ConclusionsAmong initially normoglycemic individuals, higher baseline BMD was associated with higher risk of incident prediabetes during 5 years of follow-up.