Background <p>This study aimed to explore the effects of hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise on weight loss and diabetes remission in adults with obesity and newly diagnosed prediabetes/type 2 diabetes (T2D).</p> Methods <p>Participants with obesity and newly diagnosed prediabetes or T2D (<i>n</i> = 61) were randomly allocated to standard treatment group (conventional medication and lifestyle guidance for 12&#xa0;months) and intensive treatment group (in addition to conventional medication, a high protein diet and moderate exercise were given for 12&#xa0;months).</p> Results <p>By month 12, 60 (98.4%) participants completed the 12-month follow-up visit. In the intensive treatment group, 73.33% patients in the prediabetes subgroup returned to normoglycemia and the diabetes remission rate was 86.67% in the diabetes subgroup, which were much higher than the remission rate of prediabetes subgroup (7.69%) and diabetes subgroup (16.67%) in the standard treatment group (<i>P</i> &lt; 0.001). The mean weight change was − 19.29&#xa0;kg (95% CI, − 22.95 to − 15.63) in the intensive treatment group and − 1.52&#xa0;kg (95% CI, − 5.12 to 2.07) in the standard treatment group from baseline after intervention. The weight change between the two groups was significantly different (net difference, − 17.77&#xa0;kg; 95% CI, − 22.90 to − 12.64; <i>P</i> &lt; 0.001). Percent of body fat, visceral fat area, and hepatic controlled attenuation parameter value reduced significantly in the intensive treatment group compared to the standard treatment group (<i>P</i> &lt; 0.001).</p> Conclusions <p>Hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise could lead to a considerable proportion of patients with diabetes achieving diabetes remission.</p> Trial registration <p>chictr.org.cn ChiCTR2100044305.</p>