Chapter Headings
While the “Remission of Type 2 Diabetes” chapter within the Diabetes Canada Clinical Practice Guidelines provides a synthesis of the evidence regarding diabetes remission, this accompanying user’s guide is intended to provide practical support to the health-care provider (HCP) to apply this evidence in clinical practice.
Recent studies show that remission of type 2 diabetes may be possible in a subset of individuals using a variety of interventions, including bariatric surgery (1,2), and low-calorie diets with (3,4) or without (5-7) large increases in physical activity. Of note, remission is not synonymous with cure. Rather, the term remission is chosen to reflect the often temporary resolution of hyperglycemia and subsequent possible relapse with progression of type 2 diabetes.
However, because the possibility of remission exists for some people, an ethical dilemma presents when caring for an adult with type 2 diabetes. What discussion would we have with the person who asks us about diabetes remission? Or, perhaps even more complex, with whom should we, as HCPs, start the conversation about diabetes remission? How do we continue to provide compassionate care, without discrimination, racism, oppression and stigma, particularly pertaining to body size, when discussing a management plan for type 2 diabetes, that may or may not include diabetes remission? It was in response to these questions that the resources within this User’s Guide were created.
Figure 1 illustrates remission in the context of the overall management approaches recommended for a person with type 2 diabetes, with the background of decline in beta-cell function over time. This schematic overlays the various stages of diabetes management, including prevention and diagnosis, and highlights the potentially optimal timeframe for the consideration of remission. Prevention of type 2 diabetes is emphasized across the lifespan of an individual (11), particularly for those at increased risk (see Table 1 in the 2018 “Screening For Diabetes in Adults” chapter) (12). However, at the time of type 2 diabetes diagnosis (see Table 3 in the 2018 “Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome” chapter) (13), there may already be substantially reduced pancreatic beta-cell function. Beginning at diagnosis, evidence-informed strategies are applied to reduce the progression of diabetes complications (see the ABCDES3 tool in the Diabetes Canada Quick Reference Guide) (14), including the setting of individualized targets (see Figure 1 in the “Remission of Type 2 Diabetes” chapter) (15). With respect to remission, Figure 1 serves to support conversations with people affected by type 2 diabetes to explain the need for preserved pancreatic beta-cell function and why remission is more likely for those people who have been diagnosed with type 2 diabetes for a shorter time (specifically, if attempting remission with the low-calorie diet approach, study participants had diabetes duration of less than 6 years [6]).
Remission is a journey, not a destination. It may take a person several turns in the road before they are able to arrive at and maintain remission, and some may never get to remission. As such, it is important that the person be supported throughout (and beyond) the remission management approach by a collaborative diabetes care team, which may include a primary care provider (e.g. family doctor or nurse practitioner), dietitian, pharmacist, nurse, physical activity trainer, counsellor and endocrinologist, in addition to nurturing family and social supports.
The following resources were developed with the intention of supporting conversations about diabetes remission:
Behaviour is the result of capability, opportunity and motivation. HCPs could review the domains with a person with type 2 diabetes to help determine the suitability for remission and/or to identify which domain(s) the person needs reinforcing to support the person in their management plan for remission.
FAQs
Is remission possible?
Recent studies show that remission of type 2 diabetes may be possible in a subset of individuals using a variety of interventions, including bariatric surgery (1,2), and low-calorie diets with (3,4) or without increased physical activity (5-7) (see FAQ, “Who may be a good candidate for remission of type 2 diabetes?”). Because the studies demonstrate that remission of type 2 diabetes is achieved through interventions that require a substantial, prolonged commitment, relapse is possible. As such, careful assessment must be given to people living with eating and/or mental health disorders, and concurrent medical conditions should be addressed when considering discussions regarding remission of type 2 diabetes. Remission is a journey, not a destination. It may take a person several tries before they are able to arrive at and maintain remission, and some may never get to remission. For these reasons, it is important that the person be supported throughout (and beyond) the remission management approach by a collaborative diabetes care team.
Is remission equal to a cure/reversal?
Remission is not a cure. Rather, it is temporary resolution of hyperglycemia that is frequently temporary, with subsequent possible relapse and progression of type 2 diabetes. Remission can be considered as an approach to the management of type 2 diabetes and/or can be incorporated in a management plan for type 2 diabetes, which would include deprescribing any existing antihyperglycemic therapies and incorporating therapies that can induce remission. Remission, in itself, is not a SMART (Specific, Measurable, Achievable, Realistic and Timely) goal, and HCPs are reminded to support people with inclination and circumstances for remission with the development of SMART goals for remission-inducing interventions through shared decision-making. For example, in preparation for starting phase 1 of the “Low-Calorie Diet for Remission of Type 2 Diabetes” (Figure 5), a SMART goal might be: Before my follow-up appointment with my diabetes care team, I will purchase and taste test 3 of the 6 suitable meal replacement shakes available in Canada.
What are the potential benefits of remission?
As no randomized controlled trials have evaluated the association of type 2 diabetes remission on hard outcomes, such as cardiovascular events, kidney failure or mortality, the estimated benefits of type 2 diabetes remission are related more to having target A1C levels in the normal range with or without sustained weight loss with no available evidence on improving health outcomes at present. Consistent within the guidelines, and as demonstrated in Figure 1 in Diabetes Canada's “Remission of Type 2 Diabetes” chapter, studies show that adults with type 2 diabetes who target an A1C ≤6.5% will benefit from a reduced risk of chronic kidney disease and retinopathy. This benefit is expected regardless of the person’s management plan, i.e., whether through remission or through pharmacologically-managed type 2 diabetes. Similarly, through remission, if initial body weight was reduced by 5% to 10%, studies show beneficial effects on health such as improved insulin sensitivity, hypertension and dyslipidemia management (17-19). For more information, please see the FAQs, “What is the difference between being in remission of type 2 diabetes and being pharmacologically-managed with the safe achievement of near-normoglycemia?” and “What is success? If a person has the intention for remission of type 2 diabetes and is unable to stop their antihyperglycemic medications and/or have or maintain A1C targets in the remission range, is this failure?”
Specific to the absence of antihyperglycemic medications, the potential clinical benefits of remission may include reduced cost of medication and no concern about medication side effects/interactions. Further, from a psychosocial perspective, it is postulated that remission may offer people with type 2 diabetes hope, choice and encourage self-efficacy.
Because remission may be a temporary state of uncertain (and wide-ranging) duration, the potential benefits of remission are likely to be highly variable between individuals. The long-term benefits of remission are currently unknown.
What are the potential harms of setting a management plan of remission?
By definition, to be in remission of type 2 diabetes, a person should not be taking any antihyperglycemic pharmacotherapy that is indicated in the management of type 2 diabetes. Theoretically, there is the potential for harm if a person in a high-risk population—i.e. an individual with established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), heart failure (HF) and/or over 60 years old with 2 or more cardiovascular (CV) risk factors—chose to refuse cardiorenal protective medications. Because people at high risk would benefit from organ-protective medications, they should continue these antihyperglycemic medications, even in normoglycemia, see recommendation #1 of the Diabetes Canada “Remission of Type 2 Diabetes” chapter (15).
Remission of type 2 diabetes generally requires a substantial commitment for the individual to engage in a prolonged health behavioural intervention. As such, there is potential negative impact on the person if they are not able to realize and/or sustain the management plan of remission. This risk of relapse—i.e. return of glucose levels above diabetes thresholds, with or without weight regain—presents potentially profound psychosocial harms, including stigma, reduced self-efficacy and depression.
In an attempt to minimize potential harms to a person who has the intention for remission of type 2 diabetes, HCPs are encouraged to be cognizant of language. Please refer to the “Language Matters—A Diabetes Consensus Statement” (20) and consider using the communication and shared decision-making tools provided in this User’s Guide. HCPs supporting people with a management plan of remission of type 2 diabetes are encouraged to develop processes for recall and follow-up appointments to ensure timely review and assessment of care plans.
Who may be a good candidate for remission of type 2 diabetes?
Remission is more likely for individuals with early type 2 diabetes (e.g. current studies using the low-calorie diet approach enrolled people with duration of type 2 diabetes less than 6 years); with overweight or obesity; with inclination and circumstances to engage in weight loss; and who are not using insulin therapy. Careful assessment must be given to people living with eating and/or mental health disorders, and concurrent medical conditions should be addressed when considering remission of type 2 diabetes. Remission, involving the absence of all antihyperglycemic medications, would not be recommended for individuals living with diabetes with concurrent ASCVD, HF and/or CKD or for people over 60 years old with 2 or more CV risk factors because specific antihyperglycemic agent(s) are indicated for renal or CV protection in these scenarios, even in normoglycemia. See recommendation #1 of the Diabetes Canada “Remission of Type 2 Diabetes” chapter (15) and recommendations #9 and #10 of the Diabetes Canada “Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 Update” (21).
What are the options for a management plan of remission of type 2 diabetes?
There are currently 3 therapeutic approaches which have demonstrated remission of type 2 diabetes: bariatric surgery (1,2), a low-calorie (∼800-850 kcal/day) total dietary/meal replacement diet (6,7) and a structured exercise program combined with a calorie-restricted diet (4,22). Figure 5 is an example of a low-calorie diet approach to remission of type 2 diabetes, whereas an example of a structured exercise program combined with a calorie-restricted diet can be found in the paper by Ried-Larsen et al (22). Of note, HCPs should manage people’s expectations as, within these studies, typically for health behavioural interventions, only half, or less, of participants had an outcome of remission, whereas the remission rates post bariatric surgery appear to be generally more favourable in the published literature.
The best predictors of remission are a shorter duration of type 2 diabetes and sustained weight loss of ≥15 kg of initial body weight. Thus, other health behavioural interventions that result in significant and prolonged weight loss could theoretically induce remission of type 2 diabetes. However, no recommendations are formulated in the Diabetes Canada “Remission of Type 2 Diabetes” chapter based on Mediterranean or low-/very-low-carbohydrate diets, as these studies did not meet the predefined level of evidence.
What is the difference between low-energy, low-calorie and low-carbohydrate diets?
The 2 behavioural intervention trials, DiRECT (6) and the Diabetes Intervention Accentuating Diet and Enhancing Metabolism-I (DIADEM-I) trial (7)—which have the strongest evidence for remission, to date—used low-energy diets involving meal replacement products in their study protocol. As energy is measured in calories, DiRECT and DIADEM-I are, by definition, low-calorie diets.
We ingest energy from macronutrients: carbohydrates, protein and fat. Although the better-quality research focused on meal replacement shakes used in clinical trials, there are growing accounts of people adopting low-carbohydrate meal plans (with or without a reduction in caloric content) as an approach to type 2 diabetes remission. Although, no recommendations regarding low- or very-low carbohydrate diets are formulated in the Diabetes Canada “Remission of Type 2 Diabetes” chapter (due to the studies not meeting the predefined level of evidence), the Diabetes Canada low-carbohydrate position statement did recognize that low-carbohydrate food patterns support weight loss, improve achievement of glycemic targets and/or reduce the need for antihyperglycemic therapies (23).
If the DiRECT trial protocol used a low-calorie diet of ∼800-850 kcal/day, why doesn’t the Diabetes Canada “Remission of Type 2 Diabetes: User’s Guide” use the same protocol?
DiRECT is a UK study with a protocol of a ∼800-850 kcal/day diet in phase 1 (6). This study’s intervention was adapted for Canadian use in the User’s Guide due to the Canadian Food Inspection Agency setting a minimum daily caloric intake of at least 900 calories for full meal replacements (16). Figure 5 outlines this adapted approach.
What is the difference between being in remission of type 2 diabetes and being pharmacologically-managed with the safe achievement of near-normoglycemia?
In both scenarios, the person would have achieved glycemic targets. However, in the case of the person with pharmacologically-managed type 2 diabetes, as opposed to remission, the person would remain on antihyperglycemic pharmacotherapy.
Using the ABCDES3 tool (14) as a guide, the HCP can support a person in a multi-factorial management plan to prevent or delay diabetes complications. If, in both scenarios—the person in remission and the person pharmacologically-managed with the safe achievement of near-normoglycemia—the A1C was ≤6.5%, then studies show, as demonstrated in Figure 1 of the “Remission of Type 2 Diabetes” chapter (15), that individuals would have successfully taken action to reduce their risk of complications, particularly CKD and retinopathy. Similarly, if Blood pressure (BP) and Cholesterol targets are met, then individuals in both scenarios have modified these risk factors and reduced their risk of complications of diabetes. Finally, if individuals in both scenarios remain on indicated Drugs for cardiovascular protection (particularly, the person trying for remission does not discontinue medications indicated for cardiorenal protection), then, again, the evidence demonstrates that individuals have supported themselves in applying multi-factorial management to prevent/delay complications. The ABCDES3 tool (14) can be used to support the person living with (remission of) type 2 diabetes to minimize all modifiable risk factors, thereby reducing and/or delaying diabetes complications.
Perhaps, the “Potential Goals and Approaches for Type 2 Diabetes” (Figure 1) best demonstrates what is known and not known about the differences in these 2 management approaches. Beyond diagnosis of type 2 diabetes, we know that we can prevent and delay complications by applying a multi-factorial management approach—i.e. the ABCDES3 tool (14). However, it is unknown which intervention, if any, will slow the rate of pancreatic beta-cell decline—i.e. Do antihyperglycemic therapies preserve the pancreatic beta cell more than remission or vice versa? This concept is depicted in Figure 1 with a constant downward slope of beta-cell decline.
Once a person has their type 2 diabetes in remission and has stopped all of their antihyperglycemic medications, should we also discontinue the antihypertensives and cholesterol-lowering medications?
The approach to management with antihypertensive and cholesterol-lowering medications remains consistent throughout the management of a person with type 2 diabetes (with or without remission).
First, if BP and cholesterol values are above target, then antihypertensives (24) and cholesterol-lowering medications (25) remain indicated and should be continued and/or advanced to achieve the recommended targets. Note that angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy is recommended as initial management of hypertension for people with CV disease or CKD, including albuminuria, or with CV risk factors in addition to diabetes.
Second, if BP and cholesterol values are at target, then antihypertensives and statin therapy should be continued, if indicated for CV and renal protection (see the Diabetes Canada 2020 Quick Reference Guide: Which cardiovascular non-antihyperglycemic medications are indicated for my patient?) (26). Despite a person’s remission status, both ACE inhibitors (or ARB) and statins are indicated for cardiorenal protection for:
With respect to ACE inhibitor or ARB therapy for CV and renal protection in the primary prevention of a person 55 years and older with BP values at target, the HCP may have to use clinical judgment, taking into consideration individualized risk-benefit analysis, personal preferences and medication tolerability.
Additionally, statin therapy is indicated for cardiorenal protection for:
What is success? If a person has the intention for remission of type 2 diabetes and is unable to stop their antihyperglycemic medications and/or have or maintain A1C targets in the remission range, is this failure?
With the intent of providing compassionate care, without discrimination, racism, oppression and stigma, particularly pertaining to body size, HCPs are generally cautioned to avoid any connotation to success and, by extension, failure, when discussing remission of type 2 diabetes. Being cognizant of the impact of language on a person’s health outcomes, HCPs are encouraged to apply the Diabetes Canada “Language Matters—A Diabetes Consensus Statement” in practice (20). When engaging a person in shared decision-making conversations about remission of type 2 diabetes, HCPs can use the resources provided in this User’s Guide, such as the COM-B model, to identify and develop a person’s domains to increase self-efficacy. The “5As” and the “Shared Decision-Making Checklist” were also developed to support safe conversations about remission.
Providing potential harms of remission are mitigated (see FAQ “What are the potential harms of setting a management plan of remission?”), the journey of remission may have many health benefits, even if remission is not actually realized. When a person is able to lower their A1C without increasing the risk of hypoglycemia, achieving an A1C closer to target thresholds, this may reduce the risk of diabetes complications (27,28). Similarly, through the approach of remission, if the person were to experience modest weight loss—i.e. 5% to 10% of initial body weight—that person may benefit from a substantial improvement in insulin sensitivity, hypertension and dyslipidemia management, and achievement of glycemic targets (17-19).
Should HCPs use these new definitions to fill out insurance forms: life, travel, etc.?
Remission of type 2 diabetes is not a cure, nor is it a “diagnosis”. HCPs need to exercise caution when completing insurance forms and when considering the term “type 2 diabetes in remission,” particularly as this may be a temporary state with a high-relapse rate. However, anecdotal experience has observed some individuals who have maintained remission for several decades. It is vital for HCPs to advocate for people affected by diabetes and to use the term “remission” where professional judgment determines it is appropriate. It is also important for individuals with type 2 diabetes in remission to stay connected with their diabetes care team for ongoing support and monitoring for timely evaluation and implementation of a relapse management plan.
The following 3 cases provide examples of people you may encounter in your practice who show either a high, intermediate or low potential for remission. Each case illustrates how to use the tools provided in this guide, and gives examples of how to discuss remission with people with type 2 diabetes, as well as suggested management paths.
CASE #1
Mary is a 50-year-old female. Her case suggests a HIGH potential for remission of type 2 diabetes.
Notes:
Scenario:
Mary arrives at her routine diabetes visit. To date, there has been no previous discussion of remission.
Question #1.
What are the considerations when initiating a discussion about remission of type 2 diabetes with Mary?
Question #2.
Now that you have decided to proceed with the discussion, how would you initiate the conversation?
Question #3.
What advice would you provide as a management plan?
Scenario: 3 months later
Mary has completed phase 1 of the “Low-Calorie Diet for Remission of Type 2 Diabetes” (Figure 5).
Question #1.
What do you do next?
Notes:
Question #2.
In a shared-care decision discussion, Mary decides she would like to continue to pursue remission and asks what to do next.
Scenario: 3 months later
Mary has completed phase 2 and has moved into the maintenance phase of the “Low-Calorie Diet for Remission of Type 2 Diabetes” (Figure 5) 1 month ago.
Notes:
Question.
Is Mary’s type 2 diabetes in remission?
Scenario: 6 months later
Mary returns for a follow-up appointment 6 months after stopping metformin.
Notes:
Question #1.
Mary asks whether she has cured her diabetes?
Question #2.
What is your follow-up plan now?
CASE #2
Farah is a 55-year-old female. In this case, it is advised to proceed with CAUTION when considering remission of type 2 diabetes.
Notes:
Scenario:
Farah arrives at her routine diabetes visit. She is frustrated and tired of injecting insulin 4 times daily. She is asking today if she can stop all of her insulin injections.
Question.
What are the considerations when initiating a discussion about remission of type 2 diabetes with Farah?
Scenario:
Farah returns 3 months later. She has increased her GLP1-RA as directed and is tolerating it well, but is worried as she is experiencing occasional post-meal mild to moderate hypoglycemia with adrenergic symptoms, which she treats appropriately. She has met with the bariatric team, and has decided to proceed with surgery which has been scheduled 3 months from today. Farah also expresses an interest in increasing her activity levels as her osteoarthritis has improved substantially.
Notes:
Question #1.
What medication adjustments would you consider as next steps?
Question #2.
How would you counsel Farah in regards to her exercise? She also asks if there are any “apps” you could recommend that may help her put her type 2 diabetes in remission.
Scenario:
Farah returns 1 month following successful bariatric surgery. Her bariatric team has discontinued all prandial insulin and her GLP1-RA.
Notes:
Question.
Farah asks about her BP and cholesterol medication. She is not experiencing any symptoms of low BP, but is wondering if she needs the perindopril now that her BP is normal.
CASE #3
Surinder is a 42-year-old male. His case suggests that remission with elimination of antihyperglycemic agents is NOT RECOMMENDED, but pharmacologically-managed type 2 diabetes with an A1C target of ≤6.5%—without needing to add further antihyperglycemic agents—may be considered given his co-morbidities.
Notes:
Scenario:
Surinder arrives at his routine diabetes visit. To date, there has been no discussion of remission, but he has read about this in a news article and would like to discuss the topic with you today.
Question #1.
How do you answer Surinder’s question?
Question #2.
How do you proceed in advising Surinder on next steps?
Scenario:
Surinder returns after 1 month. He has lost some weight and, while he has been able to mostly follow the “Low-Calorie Diet for Remission of Type 2 Diabetes” (Figure 5) phase 2 plan, he has had occasional setbacks, especially on the weekends. He still wants to continue, but worries he may not realize his desired outcome.
Question.
How do you proceed?
Scenario:
Surinder has now completed 3 months of phase 2 of the “Low-Calorie Diet for Remission of Type 2 Diabetes” (Figure 5).
Notes:
Question.
Surinder is very curious to know—Is his type 2 diabetes in remission?
Scenario:
Surinder returns 3 months later (6 months after initiating the diabetes remission conversation).
Notes:
Question #1.
Surinder asks about his BP and cholesterol medication. He is not experiencing any symptoms of low BP, but is wondering if he needs the perindopril now that his BP is normal.
Question #2.
What’s next for Surinder?
The authors are particularly grateful for the organizational, communication and editorial skills of Tracy Barnes, who has contributed extensively to the quality of this manuscript. Thank you also to Jill Toffoli for her help editing and preparing the manuscript, in particular, her design work on the tables and figures.
S.J. reports consulting and/or speaking honoraria from Abbott, AstraZeneca, Dexcom, Eisai, GlaxoSmithKline, Novo Nordisk, Pfizer and Roche, as well as funded clinical research with Novo Nordisk; H.S.B. reports research funding or trial fees paid to his institutions by Amgen, AstraZeneca, Boehringer Ingelheim, Canadian Institutes of Health Research (CIHR), Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals Co. Ltd, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Public Health Agency of Canada, Sanofi, and Tricida, outside the submitted work, as well as speaking honoraria from American Diabetes Association, Canadian Hypertension Education Program (CHEP+), Canadian Society of Endocrinology & Metabolism (CSEM), Endocrine Society, International Diabetes Federation, LMC Physicians Inc., Medscape, Optum, Center for Advanced Clinical Solutions, and Windsor Heart Institute; A.-S.B. reports speaker fees from Dexcom Canada and holds research funds from CIHR, JDRF, Société Francophone du Diabète, Diabète Québec, Fonds de recherches du Québec en Santé; D.M. reports research funding to his institution by CIHR, the Kidney Foundation of Canada, Mitacs Inc, NorWest Co-op Community Health, PepsiCo Inc, The Weston Family Foundation, and the Winnipeg Foundation, outside the submitted work; M.V. reports ad boards and consultations with Abbvie, Abbott, Bausch Health, Lifescan, Lyceum, Novo Nordisk, Roche and Sanofi, speaking fees for Abbott, Abbvie, Bausch Health, Lifescan, Lilly, Merck, Novo Nordisk, Pfizer, Roche and Sanofi, and investigator-driven research funding from Novo Nordisk, Bausch Health and Abbott; S.M.R. reports consulting fees from Abbott, Novo Nordisk, Bayer, Eli Lilly, Janssen and the Canadian Collaborative Network and speaker fees from Abbott, Novo Nordisk, Eli Lilly, Janssen, Sanofi, AstraZeneca and McMaster University; B.M. has no conflicts to disclose.
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