It is well-demonstrated that lifestyle changes, such as decreased caloric intake and increased physical activity leading to weight loss can decrease the incidence and progression of DM 
. In this study, we examined the magnitude of weight loss associated with the reduction of dose or discontinuation of anti-diabetic medications in a selected sample of patients with DM who attended 2 University-based weight management centers. While a number of previous studies suggest that weight loss often leads to diminished need for anti-diabetic medications 
we are not aware of any previous study that aimed to quantify the magnitude of weight loss associated with an improvement in blood sugars sufficient to warrant a decrease in dose, or discontinuation of anti-diabetes medications. Though trials like Look AHEAD have analyzed the economic impact of anti-diabetic drug dose reductions consequent to weight loss 
, our observational study appears to be the first to identify the association between the magnitude of the weight loss and dose reductions or discontinuations of anti-diabetic medications.
This retrospective cohort study found that the selected patients achieved 14.2% mean weight loss at one year, and 11.1% at study conclusion (30.2 months mean follow-up), respectively (). The high magnitude of weight loss is not necessarily surprising given that this sample was selected to identify those patients who were successful enough in their lifestyle changes to be able to lower the dose or discontinue at least one anti-diabetic medication. Further, by virtue of being enrolled in a University-based, comprehensive weight management center program, they each had access to an intensive, multi-specialist support team that utilized state-of-the-art weight management tools and techniques. 44% of these patients with type 2 diabetes successfully discontinued one or more of their anti-diabetes medications. On average, 11.2% of initial body weight loss was required to achieve this ().
We observed that the percentage weight loss that was associated with discontinuing or reducing the dose of insulin was lower than that for sulfonylureas. The fact that insulin is shorter acting than sulfonylureas, and that insulin involves injections, may have prompted the treating physicians to discontinue insulin earlier than sulfonylureas. Also, we observed that none of the patients in our cohort discontinued metformin or had even a single dose reduction. The reason for this is likely that the treating physicians preferred retaining metformin for its weight-reducing and insulin resistance-decreasing properties, rather than for its effect on glycemia 
. In additional, because there is minimal risk of hypoglycemic effects with metformin, compared with insulin or sulfonylureas, less aggressive discontinuation of metformin may be preferred.
Also, it is encouraging to note that 3 of the 4 different classes of anti-diabetic medications used in our study could be dose reduced/discontinued with weight loss. Hence it should be emphasized that, irrespective of the type of anti-diabetic medication and its mechanism of action, weight loss indeed helps in dose reduction/discontinuation and hence should be uniformly prescribed to overweight and obese patients with type-2 diabetes mellitus.
Our observation that 50 patients (study cohort) who could lose weight were also successful in dose reductions/discontinuation of anti-diabetic medications while only 3 who lost weight were unsuccessful in dose reductions/discontinuation of anti-diabetic medications is encouraging.
Our study participants in the morbidly obese category showed some interesting differences. They tended to have poorer cardiovascular risk profiles at baseline, and achieved lesser reduction of body weight, blood pressure, and lipid levels (, and ). Also, while some had dose reductions, none was successful in discontinuing any of their anti-diabetes medications. The possible reason for this observation could be that the participants in the morbidly obese category had a higher HbA1c% at baseline (). Though they did achieve significant reduction in their HbA1c% at study exit () this may not have been sufficient to translate into discontinuation of any of the anti-diabetic medications. Hence, it may be reasonable to hypothesize that greater magnitudes of weight loss may be required for the participants in this group to discontinue anti-diabetic medications when compared to the participants in the other BMI categories.
Evidence from observational studies and clinical trials has clearly shown that morbidly obese patients with type 2 DM benefit from bariatric surgery 
. Nearly 50–80% of these patients achieved complete remission of diabetes. When followed, prevalence of diabetes decreased at 2 years, 8 years and even after 10 years after surgical intervention in these patients 
. Further, bariatric surgery provided sustained improvement in quality of life and significantly reduced mortality 
. At the end of 2 years, in a clinical trial setting, surgically treated patients had lost 20% of their body weight and reduced their HbA1c% by 2.5 
. However, in our study, morbidly obese patients lost a lesser amount, 7.2% of their body weight, and reduced HbA1c% by 0.2 by study exit (). In addition to reduction in insulin resistance, bariatric surgery is known to increase incretins like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which lead to improved beta-cell function 
. This may help explain the dramatic and sustained response that bariatric surgery can achieve in the morbidly obese when compared to average results using medical management. Diabetes management has moved from a guidelines-based approach to an individualized approach that takes factors such as age, comorbidities, diabetes-associated complications, symptoms and patient satisfaction into account in deciding on treatment choices and doses 
. In a recent review by Ismail-Beigi et al., the authors described the superiority of individualized diabetes management over guideline-based diabetes management after pooling multiple trial data 
. Consistent with this novel approach, our study, which was based on individualized and comprehensive management of obese diabetic patients, took the overall clinical profile of the patient, rather than any single factor into making treatment choices. Hence, the results of our study may be applicable to any physician-supervised, outpatient weight management approach. It is encouraging that success at decreasing and discontinuing anti-diabetic medications was achieved with relatively modest weight loss, and that even a medication with a very substantial impact on patient health-related quality of life - insulin 
- was discontinued at levels of weight loss that can often be achieved in physician-guided settings.
Small sample size is an important limitation of our study that decreased the precision of our estimates and prevented us from examining effect modification attributable to gender, race and BMI categories. The retrospective cohort design limits our data to whatever is recorded in patient case records. The convenience sampling strategy, including only those obese patients with diabetes who successfully achieved at least one dose reduction of their anti-diabetic medications may have introduced a selection bias, by selecting individuals who were well motivated or consistent in their attendance at follow-up visits, and thus may not be representative of all clinic attendees, or all patients with type-2 diabetes. Missing data was another limitation. Though we used statistical adjustments, it is still possible that the estimates might have been biased due to these missing data. Also, it would have been interesting to compare our study cohort with patients who had significant weight loss but were unsuccessful in dose reductions/discontinuation of anti-diabetic medications. We were unable to do this analysis as we had only 3 patients in this category.
In conclusion, among the obese patients with type 2 diabetes studied, intentional weight loss of a mean magnitude of 7–14% was typically required for full discontinuation of at least one anti-diabetic medication. Discontinuation of insulin was achieved at a mean weight reduction of 11% of starting body weight. Successful reduction in dosage of anti-diabetes medications was typically achieved with a lesser, 4–7% weight loss. Also, with just 5% weight loss, doses of sulphonylureas, insulin and any of the anti-diabetic medications could be reduced by 39%, 42% and 49% respectively. Knowledge of the modest magnitude of weight loss typically required to successfully reduce medication use among overweight and obese patients with type 2 diabetes may be helpful to health care providers and patients alike.