On the discussion board, using a minimum of two articles that are supporting your PICOT question, submit one paragraph synthesizing the research into clear, concise statements without separately revie

Original Research Effects on Diabetes Medications, Weight and Glycated Hemoglobin Among Adult Patients With Obesity and Type 2 Diabetes: 6-Month Observations From a Full Meal Replacement, Low-Calorie Diet Weight Management Program Judy Y. Shiau MDCM, FRCPC, DipABOM a,*,Derek Y.F. So MD, FRCPC, FACC b, Robert R. Dent MDCM, FRCPC c aLEAF Weight Management Clinic, Division of Endocrinology and Metabolism, University of Ottawa, Ottawa, Ontario, CanadabDivision of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, CanadacWeight Management Clinic, Ottawa Hospital, Division of Endocrinology and Metabolism, University of Ottawa, Ottawa, Ontario, Canada Key Messages •Patients with obesity and diabetes may require intensive strategies for weight management to overcome the barrier of weight- gaining diabetes medications.

•A full meal replacement, low-calorie diet in a 6-month weight management program can achieve up to 18.6% weight loss in patients with diabetes.

•Within this full meal replacement, low-calorie diet program, medications for diabetes can be signiﬁcantly reduced while con- comitantly achieving good glycemic control. article info Article history:Received 24 January 2017 Received in revised form 12 March 2017 Accepted 15 March 2017 Keywords:

diabetes low-calorie diet meal replacement medication changes weight loss abstract Objectives:A 6-month weight-management program with full meal replacement, low-calorie diet (full MR-LCD) (900 kcal/day for 6 to 12 weeks) follows a protocol for patients with diabetes for decreasing or discontinuing weight-gaining diabetes medications ﬁrst (Group WG) and then titrating weight-neutral medications (Group WN).

Methods:This is a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes who were taking medications.

Results:Group WG and Group WN were similar at baseline, except that glycated hemoglobin (A1C) levels were signiﬁcantly lower in Group WN (7.5% vs. 6.6%; p<0.001). At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92.1% sulfonureas, 86.5% insulins, 78.8% thiazolidinediones, 77.8% alpha-glucosidase inhibitors, 50% meglitinides, 33.3% dipeptidyl peptidase-4 (DPP-4) inhibitors and 32.8% metformin. At 6 months, compared with baseline, A1C levels improved in Group WG and Group WN (6-month A1C levels 6.7% and 5.8%, respectively; p<0.0001), and Group WN had signiﬁcantly better A1C levels than Group WG. At 6 months, 30% of patients were no longer taking diabetes medications and had signiﬁcantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002); both groups had improved glycemic control at 6 months (A1C 6.0% vs. A1C 6.6%; NS).

Conclusions:In patients with obesity and type 2 diabetes taking medications, a full MR-LCD program appears to be safe and includes improvement in A1C levels. At 6 months, the percentage of weight loss can be signiﬁcantly better in patients who no longer require diabetes medications, and A1C levels are best con- trolled in patients who are on WN medications.

E-mail address: [email protected] Can J Diabetes 42 (2018) 56–60 Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage:

The Canadian Diabetes Association is the registered owner of the name Diabetes Canada.

https://doi.org/10.1016/j.jcjd.2017.03.006 Mots clés :

diabète régime hypocalorique substitut de repas changements de médicaments perte de poids résumé Objectifs :Un programme de prise en charge du poids d’une durée de 6 mois par une substitution complète des repas-régimes hypocaloriques (SR complète-RH) (900 kcal/jour durant6à12semaines) utilise un protocole destiné aux patients diabétiques pour diminuer ou interrompre les antidiabétiques qui entraînent la prise de poids (groupe PP) et ensuite ajuster la dose des médicaments qui sont sans effet sur le poids (groupe SEP).

Méthodes :Il s’agit d’une étude de cohorte rétrospective (de 1992 à 2009) sur le poids, la régulation de la glycémie et les changements d’antidiabétiques chez 317 patients souffrant d’obésité et de diabète de type 2 qui prenaient des médicaments.

Résultats :Au début, le groupe PP et le groupe SEP avaient des caractéristiques similaires, à l’exception de l’hémoglobine glyquée (A1c) qui était signiﬁcativement inférieure dans le groupe SEP (7,5 %vs6,6 %; p<0,001). Après 6 mois, les deux groupes avaient perdu 16 % de leur poids; la diminution ou l’interruption des médicaments étaient de 92,1 % pour les sulfonylurées, 86,5 % pour l’insuline, 78,8 % pour les thiazolidinediones, 77,8 % pour les inhibiteurs des alpha-glucosidases, 50 % pour les méglitinides, 33,3 % pour les inhibiteurs de la dipeptidyl peptidase-4 (DPP-4) et 32,8 % pour la metformine. Comparativement au début, les concentrations d’A1c après 6 mois s’amélioraient dans le groupe PP et dans le groupe SEP (des concentrations respectives de l’A1c après 6 mois de 6,7 % et de 5,8 %; p<0,0001), quoique le groupe SEP avait des concentrations d’A1c signiﬁcativement meilleures que le groupe PP. Après 6 mois, 30 % des patients ne prenaient plus d’antidiabétiques et montraient un pourcentage de perte de poids signiﬁcativement meilleur que ceux qui prenaient des médicaments (18,6 %vs16 %; p=0,002); la régulation de la glycémie s’était améliorée chez les deux groupes après 6 mois (A1c de 6,0 %vsA1c de 6,6 %; NS).

Conclusions :Chez les patients souffrant d’obésité et de diabète de type 2 qui prennent des médicaments, un programme de SR complète-RH semble démontrer son innocuité et apporte l’amélioration des con- centrations de l’A1c. Après 6 mois, le pourcentage de perte de poids peut être signiﬁcativement meilleur chez les patients qui n’ont plus besoin d’antidiabétiques, alors que les concentrations d’A1c sont mieux maîtrisées chez les patients qui prennent des médicaments SEP.

© 2017 Canadian Diabetes Association. Introduction Obesity and diabetes are strongly associated. Both are chronic diseases that are progressive and diﬃcult to treat. Overweight and obesity constitute an estimated 80% to 90% of persons with type 2 diabetes (1) and, in type 1 diabetes, there has been a 7-fold increase in obesity over 20 years (2) . Treatment of obesity in patients with diabetes is further complicated by the fact that some glucose- lowering medications, such as insulin, are associated with weight gain (3,4) . Conversely, weight loss improves glycemic control by increasing insulin sensitivity and glucose uptake and reducing hepatic glucose output (4) .

Accordingly, achieving normoglycemia in patients with diabe- tes requires a balance of both weight management and selection of appropriate diabetes medications. In general, the principle of weight reduction is to follow a lower caloric diet that is sustain- able (5) . In patients with type 2 diabetes, hypoglycemic agents that involve the potential for weight gain may reduce the rate of weight loss (6) . Therefore, for management of weight in patients with type 2 diabetes, a balance must be established between sustainable diets and the use of medications for glycemic control.

Meal replacements (MRs) show strong evidence as being a good tool for weight management (7) . MRs have been reported in patients with type 2 diabetes and have been shown to produce superior weight loss compared to individualized diet plans. This was observed irrespective of whether it was a partial MR, in which 1 or 2 meals and snacks are replaced by MRs, aiming for a 500 to 1000 daily kcal deﬁcit (8–10) , or full MRs, in which all meals are replaced with MRs as low-calorie diets (LCDs), deﬁned as 800 kcals per day or more.

The relationship between changes in hypoglycemic medications and weight loss with full MRs have been described previously in a few small cohorts of 8 to 32 patients (11–13) . The limitations of these studies include the small sample sizes, the narrow choices of hypo- glycemic agents and the severity of the diets which, in 1 study, was 425 kcals per day. The aim of our study was to determine the ben- eﬁcial effects and changes in hypoglycemic agents within a behavioural program using full MR-LCDs in patients with obesity and diabetes. We hypothesized that in a full MR, medicallysupervised weight-management program, patients with diabetes would lose weight, require less hypoglycemic medications and have improved glycemic control.

Methods A retrospective cohort study was conducted in 2744 patients con- secutively enrolled between 1992 and 2009 in the CORE program at the Ottawa Hospital Weight Management Clinic (OHWMC) in Ontario, Canada. The study protocol was approved by The Ottawa Hospital Research Ethics Board. The CORE program enrols patients with diagnosed obesity so as to assist in weight management, with the goal of improving long-term health. The CORE program is a year- long, comprehensive, intensive lifestyle behavioural program.

Intervention The ﬁrst 6 months (week 1 to week 26) include mandatory weekly group sessions led by a dietitian, behaviour therapist or exer- cise therapist and, in the last 6 months (weeks 27 to 52), patients are offered monthly support sessions, which they can choose to access. All patients receive OPTIFAST ®900 as full meal replace- ments starting at week 2. Patients consume 4 MR shakes per day for a total of 900 kcal per day, a regimen that is high in proteins (90g/day) and moderate in carbohydrates (67 g/day). Patients with initial body mass indexes (BMIs) of 33 kg/m 2or higher commit to 12 weeks of full MRs, while patients with initial BMIs below 33 start with 6 weeks of full MRs and the option to increase to up to 12 weeks of full MRs. Once patients have completed their full MR regimen, there is a 5-week transition period to regular food, typi- cally followed by a maintenance diet, as determined in a one-on- one dietitian counselling session.

Clinical care During the ﬁrst 6 months at the OHWMC, physician visits occur weekly, and medications are adjusted as needed. After 6 months, J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–6057 patients may attend monthly support groups, but follow up with the OHWMC physician is booked as needed with respect to weight management. Patients return to their primary care physicians at 6 months for ongoing regular medical monitoring, including man- agement of diabetes medications.

For patients with type 2 diabetes who are on full MR, the clinic protocol is ﬁrst to reduce weight-gaining medications (Group WG).

Within Group WG, priority is given to decreasing medications that have hypoglycemic effects and, subsequently, other weight-gaining medications. Finally, weight-neutral medications (Group WN) may be reduced if clinically indicated. Group WG includes patients taking insulin, sulfonureas (SUs), thiazolidinediones (TZDs) and/or meglitinides. Patients in Group WG may also be on weight-neutral medications. Group WN is composed of patients taking solely metformin and alpha-glucosidase inhibitors (AGIs). The data col- lected for this study predates the availability of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors in Canada. Dipeptidyl peptidase-4 (DPP-4) inhibi- tors had just been introduced in Canada, and the rare patients who were taking DPP-4 inhibitors were also taking weight-gaining hypo- glycemic agents and, therefore, were accounted for in Group WG.

The percentage of reduction of hypoglycemic agents is at the dis- cretion of the treating physician but typically is a reduction of 30% to 50% of insulin the night prior to starting OPTIFAST ®900 shakes and a 50% reduction of medications that include risks for hypogly- cemia, such as sulfonylureas, on the day of starting OPTIFAST ®900 shakes. Patients who present with well-controlled glucose levels have more aggressive discontinuation of hypoglycemic agents in order to avoid hypoglycemia.

When patients transition back to regular food, diabetes medi- cations may once again be adjusted; the typical protocol is to avoid weight-gaining agents in Group WG and preferentially selecting or increasing medications in Group WN. However, if patients are trying to avoid insulin use and are already on maximum levels of Group WN medications, another agent from Group WG may be prescribed.

Statistical methods All data were prospectively collected in a registry. Consecutive patients with type 2 diabetes (deﬁned as fasting glucose levels of 7.0 mmol/L or higher or A1C levels of 6.5% or higher on 2 separate occasions) who had given consent to participate in the registry were included. Patients were excluded if there was noncompliance in the behavioural program, deﬁned as 1) taking less than 50% of the MRs or 2) attending fewer than 6 sessions in the program. Baseline and 6-month hypoglycemia medications, weights and glycemic pro- ﬁles were collected. The medications for patients in Group WG were compared with those for Group WN.

Categorical variables were expressed as percentages and con- tinuous variables as mean±standard deviation. Continuous and cat- egorical variables were compared between Group WG and Group WN using ANOVA and the chi-square test, as appropriate. Weight and A1C levels were compared at baseline and at 6 months, with repeated measures by ANOVA using a mixed between-within subject analysis. Medications for diabetes at 6 months were categorized as discontinued, decreased in dosage, increased in dosage or added as new agents. Missing data were imputed by using multiple impu- tations with the previous observation carried forward. Linear regres- sion modelling was conducted to account for differences in baseline demographics, which could affect weight loss. All analyses were per- formed using SPSS 18.0 statistical software (IBM, Armonk, New York).

Results Overall, glycemic data were available for 2744 patients; 456 (20.1%) were identiﬁed as having type 2 diabetes, and 91 (3.3%) ashaving impaired fasting glucose. In patients with type 2 diabetes, 95 (20.8%) were not taking medications for diabetes. Of the 361 patients (79.2%) who were taking medications for diabetes, 44 were excluded for noncompliance with the program. Of the 317 patients included in this study, 235 (74.1%) were in Group WG, and 82 (25.9%) were in Group WN.

The baseline characteristics of the 317 patients with type 2 dia- betes and taking medications are described in Table 1 . In Group WG and Group WN, there were no signiﬁcant differences in age, gender, baseline weights or initial BMIs or in patients with initial BMIs below 33 or on the 6-week or 12-week MRs. However, baseline A1C levels were signiﬁcantly lower in Group WN than in Group WG (p<0.001).

Baseline diabetes medications included 72.2% metformin, 43.8% SUs, 23.3% insulins, 20.8% TZDs, 2.8% AGIs, 1.3% meglitinides and 0.9% DPP-4 inhibitors. Decrease or discontinuation of medications over 6 months by medication classes were as follows: 92.1% SUs, 86.5% insulins, 78.8% TZDs, 77.8% AGIs, 50% meglitinides, 33.3% DPP-4s and 32.8% metformin ( Table 2 ). The only medication that was increased in dosage from baseline was metformin (3.5%), and rarely was a new medication added for glycemic control by 6 months: SUs, 6 patients; metformin, 17 patients; TZDs, 4 patients; DPP-4 inhibitors, 2 patients.

Changes in weight and A1C levels from baseline to 6 months and in diabetes medications are shown in Table 3 . Differences in baseline A1C levels between Group WG and Group WN did not affect the percentages of weight. There was no signiﬁcant difference in per- centage of weight loss between Group WG and Group WN. At 6 months, in those who continued to take diabetes medications (223 patients) compared with patients who were no longer taking medi- cations for diabetes (94 patients), the percentage of weight loss was signiﬁcantly lower (16.0% vs. 18.6%; p=0.002). Baseline versus 6-month A1C levels by groups were: 7.5% vs. 6.7% (p<0.0001) for Group WG; 6.6% vs. 5.8% (p<0.0001) for Group WN; 7.4% vs. 6.0% (p<0.0001) for patients taking no medications at 6 months; and 7.2% vs. 6.6% (p<0.0001) for patients who were still taking medica- tions. A1C levels were signiﬁcantly lower in Group WN than in Group WG (p<0.0001).

Discussion To our knowledge, the current study is the largest reported cohort concerning changes in hypoglycemic agents in patients with dia- betes following an intensive lifestyle program in conjunction with a full MR LCD diet. The key ﬁndings in our study include the following:

1. The protocol of reducing medications that are weight gaining ﬁrst and then weight-neutral medications appears to be safe, allowing for signiﬁcant improvement in A1C levels in the 6-month protocol. Table 1 Baseline characteristics of 317 patients with obesity and diabetes and taking medications Group WG (235) Group WN (82) p value Age (SD) 51.8 (9.2) 49.7 (9.9) NS Female (%) 121 (51.5%) 57 (69.5%) NS Initial weight in lbs (SD) 281.6 (58.3) 274.4 (51.5) NS Initial BMI kg/m 2(SD) 44.0 (8.6) 44.8 (7.6) NS Patients with BMI<33 (%) 8 (3.4%) 2 (2.4%) NS Patients on 6 weeks of MR (%) 26 (11.1%) 10 (12.2%) NS Patients on 12 weeks of MR (%) 209 (88.9%) 72 (87.8%) NS Baseline A1C 7.5% 6.6% p<0.001 A1C, glycated hemoglobin; BMI, body mass index; Group WG, Group weight-gain medications; Group WN, Group weight-neutral medications; MR, meal replace- ment; SD, standard deviation. J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–60 58 2. A number of diabetes medications were either discontinued or reduced, including SUs (92.1%), insulins (86.5%) and metformin (32.8%).

3. Patients who were able to discontinue all diabetes medica- tions at 6 months appeared to have greater reductions in per- centage of weight loss.

4. At 6 months, patients who were originally taking weight- neutral medications had better glycemic control than patients on weight-gaining diabetes medications.

Previous data about weight loss and glycemic control have been limited to small cohorts. Harder et al showed that a full MR-LCD of 850 kcal/day resulted in an 11% weight loss in 11 patients with obesity and type 2 diabetes at 8 weeks. However, only 4 of the 11 patients were originally taking hypoglycemic agents, and they were discontinued before MR commencement (14) . In a retrospective review by Anderson et al of 183 obese individuals who were on a full MR-LCD (800 kcal/day) but with the possibilities of increasing to 1000 kcal/day, 50 patients had diabetes. Of these patients, 44 were taking hypoglycemic agents and, with weight loss, there was a 53.8% discontinuation of medications overall and a 68% reduction of medi- cations for those who lost more than a 100 pounds (15) . A study by Collins et al of 32 patients with type 2 diabetes reported an average 14.8% reduction of initial weight after following a 12-week 800 kcal per day diet (half the patients were on full MRs, the other half were on partial MRs with food to achieve a minimum of 800 kcal per day). At 1 year, subjects maintained an average of 58.8% of the weight loss over the diet period. A1C values at baseline, week 12 (end of LCD) and 1-year follow up were, respectively, 8.4%, 6.6% and 8.1%, with no statistical differences between baseline and year 1.

At week 12, 6 of the 8 participants taking insulin discontinued that medication, while the other 2 had a 71% reduction in dosage. At 1-year follow up, 1 participant had restarted insulin. By the end of the LCD, 17 of the participants (71%) had discontinued oral hypoglycemics, and the remaining 7 subjects reduced medication needs by 75%. At the 1-year follow up, 13 of the 24 patients (54%) remained off oral hypoglycemic medications (13) . A small study by Plum et al compared 14 patients with obesity and type 2 diabetes before and after an equivalent amount of weight loss induced by either LCD (patients on full MR of 800 kcal per day) or Roux-en-Ygastric bypass (RYGB). Patients taking TZDs and insulin were excluded. There was a mean reduction of 8.1% in total body weight (7 patients on LCD at week 8; 7 patients after RYGB at week 3.4).

A1C levels were reported only at initial weight: A1C 7.8% (LCD) and 7.5% (RYGB). The disposition index (insulin secretion normalized to the degree of insulin resistance) improved in both groups, but the absolute increase was greater after RYGB. Antidiabetes medica- tions were discontinued after RYGB contrasting with a 55% reduc- tion in the number of medications after LCD (16) . Like the above ﬁndings, our study provides detailed accounts of changes in medi- cations and separates differing cohorts based on the diabetes regi- mens and their resultant responses, including percentages of weight changes and A1C levels. As hypothesized, weight and diabetes medi- cations decreased during the program, but an interesting ﬁnding was that the patients who had discontinued all diabetes medica- tions at 6 months had signiﬁcantly better weight loss, and those who were originally taking weight-neutral medications had the best resultant A1C levels at the end of the program.

Our study is also the largest assessment of patients with type 2 diabetes taking full MR-LCD in a real-world setting. Although the Look AHEAD (Action for Health in Diabetes) study included a larger patient population, a partial MR protocol was utilized in the inten- sive lifestyle intervention arm (ILI). At 1 year, the ILI arm showed an 8.5% weight loss; 25% of ILI participants were no longer prescribed diabetes medications (compared with 12% in diabetes and support education); and insulin use decreased from 15% at baseline to 13% (17) . In contrast, at 6 months, we observed an approximately 16% weight loss; 30% of patients were no longer prescribed diabetes medications; and we found insulin discontinuation or decrease of 86.5%. Although our study describes results at 6 months, evidence from randomized intervention trials supports the ﬁnding that the greater initial weight loss produced by MR diets improves long- term weight maintenance, provided it is followed by a 1- to 2-year integrated weight-maintenance program consisting of lifestyle inter- ventions that involve dietary change, nutrition education, behaviour therapy and increased physical activity (18) . Intentional weight loss of 7% to 14% may be required for full discontinuation of at least 1 hypoglycemic medication, whereas discontinuation of insulin may be achieved at a mean weight reduction of 11% of initial body weight (19) . Therefore, compared with a partial MR diet in which there can Table 2 Changes in diabetes medications Medication Baseline N (% of 317 patients)Changes in medications at 6 months compared with baseline Discontinued n (% discontinued)Decreased dosage n (% decreased)Increased dosage n (% increased) Sulfonurea 139 (43.8%) 120 (86.3%) 8 (5.8%) - Thiazolidinediones 66 (20.8%) 48 (72.7%) 4 (6.1%) - Insulin 74 (23.3%) 33 (44.6%) 31 (41.9%) - Meglitinides 4 (1.3%) 2 (50%) - - Metformin 229 (72.2%) 51 (22.3%) 24 (10.5%) 8 (3.5%) Alpha-glucosidase inhibitor 9 (2.8%) 7 (77.8%) - - DPP-4 inhibitor 3 (0.9%) 1 (33.3%) - - DPP-4, dipeptidyl peptidase-4.

Table 3 Weight and A1C levels based on medications Wt lbs baseline (SD) Wt lbs 6 mo (SD) % wt loss (SD) A1C baseline (SD) A1C 6 mo (SD) p Group WG 281.7 (58) 233.8 (48) 16.7% (6.7) 7.5% (1.4) 6.7% (1.6) p<0.0001 Group WN 274.0 (51) 227.4 (44) 16.8% (6.9) 6.6% (1.2) 5.8% (1.3) * p<0.0001 No meds at 6 months (94 patients) 281.2 (61) 227.7 ((48) 18.6% (6.5) † 7.4% (1.2) 6.0% (0.8) p<0.0001 Taking medications at 6 months (223 patients) 279.1 (55) 234 (47) 16.0% (6.7) 7.2% (1.4) 6.6% (1.6) p<0.0001 A1C, glycated hemoglobin; Group WG, Group weight-gain medications; Group WN, Group weight-neutral medications; mo, month; Wt, weight.

* A1C levels were signiﬁcantly different in Group WG and Group WN (p<0.0001). †Percentage of weight loss was signiﬁcantly greater in patients taking no medications at 6 months compared with patients still taking medications (p=0.002). J.Y. Shiau et al. / Can J Diabetes 42 (2018) 56–6059 be more variability in energy intake, in our cohort, the effect of a full MR diet on weight loss and changes in medications could be expected to be superior.

This is the ﬁrst study to categorize diabetes medications based on their weight-gaining or weight-neutral properties. This study of 317 patients with type 2 diabetes demonstrates that the protocol of reducing medications that are weight-gaining ﬁrst and then reduc- ing weight-neutral medications appears to be safe and involves no signiﬁcant compromise of A1C levels in the 6-month protocol. There were no signiﬁcant differences in weight loss between Group WG and Group WN. When comparing the 6-month changes in medi- cations, the decrease in or discontinuation of hypoglycemic agents is extensive, ranging from 50% to 92.1% for Group WG and 32.8% to 72.8% for Group WN. The signiﬁcant changes in weight at 6 months were observed, even accounting for differences between baseline A1C levels between groups. The protocol for patients with diabetes on full MR-LCD is to decrease weight-gaining and hypo- glycemic agents ﬁrst and then, only if necessary, weight-neutral hypoglycemic agents. Reintroduction of medications for glycemic control may be necessary when patients increase intake of regular food, but it has been minimal. In fact, what is impressive is that by 6 months, of patients who were taking insulin at baseline, 44.6% discontinued the medication, and 41.9% decreased the dosage. It is reassuring that despite reduction of hypoglycemic agents, glyce- mia levels improved, such that at 6 months, patients were at lower weights and had improved glycemic control, thus requiring less medication. Patients who particularly beneﬁted from the full MR-LCD were patients who were able to have all their diabetes medica- tions discontinued by 6 months (this group experienced the great- est amount of weight loss: 18.6%) and those who had initially been on weight-neutral diabetes medications (had the best A1C pro- ﬁles at the end of the program; A1C levels at 6 months were 5.8% compared with baseline levels of 6.6 %). Therefore, at the very least, glucose levels are safely maintained for patients with diabetes involved in a full MR-LCD 6-month lifestyle program and require fewer medications. This practice appears to be safe and to involve no signiﬁcant compromise of A1C levels, irrespective of the cat- egory of diabetes medications. This should reassure clinicians about the use of various classes of medications in patients entering a full MR weight-loss program.

Certainly, there are some limitations in our study. First, this is a retrospective cohort, and the rationales for choices of initial dia- betes medications cannot be elucidated. Second, our analysis was restricted to weight and glycemic control in patients with obesity and diabetes taking medications at 6 months. As patients transitioned back to the community for their diabetes manage- ment, we were unable to obtain 1-year data consistently. Although our study lacks length of follow up compared to other behavioural obesity-study interventions, it has the distinction of being the largest reported cohort of patients with diabetes taking medications who have been drawn from a signiﬁcant database of several thousand patients on a standardized full MR-LCD behavioural program. A ﬁnal limitation is that our data cannot be extrapolated to novel glyce- mic agents introduced in Canada. In 2009, there was the introduc- tion of a new class of weight-neutral medication for diabetes, DPP-4 inhibitors. In 2010 and 2015, there was the approval of a poten- tial weight-losing medication class, GLP-1 agonists, and subse- quently, in 2014, SGLT2 inhibitors. Data collected from the CORE program was limited to years before 2009 so as to mitigate the evolv- ing landscape of new hypoglycemic agents approved by Health Canada since 2010. Future analysis in the context of these novel agents will be required.Conclusions Patients who are trying to control their weight often face bar- riers that make weight management more diﬃcult. Barriers can be related to medications, mechanical problems (e.g. hernia, knee pain, sleep apnea), mood or situational effects (e.g. skipped meals, shift work). Full MR-LCD behaviour programs can be regulated for strategic breaking of the cycle that patients are caught in with respect to their weight, allowing patients to achieve lower weights and sub- sequently “reset” themselves. One signiﬁcant barrier to treatment of obesity can be weight-gaining medications for diabetes management. This study demonstrates that we can safely reduce weight-gaining medications in patients with diabetes by using a full MR-LCD behaviour program, and this can achieve signiﬁcant weight loss without compromising glycemic control.

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