Deprescription in reversed type-2 diabetes melitus
Evidence, now, abound that Type 2 diabetes mellitus can be successfully reversed, and maintained with non-pharmacological therapies1,2,3,4. Reversal of type 2 diabetes can be achieved with metabolic surgery, low-caloric diets and carbohydrate restriction4.
Patients with type 2 diabetes presenting to a lifestyle physician for disease reversal can be a newly diagnosed diabetic not yet on any medication but may also be any of those on monotherapy or multiple medications.
Medication withdrawal, and avoidance of their potential side effects is one of the key motivations for a patient to adopt aggressive lifestyle changes to reverse the disease; hence, the decision to stop all the medications or to leave some, at the lowest effective doses, must be taken by both the doctor and the patient once a successful remission or partial remission is achieved.
While deprescribing the medications is likely to be easy in those on monotherapy, it would pose some challenges in those on multiple medications.
Hence, doctors would always face the challenge of de-prescribing the medications once the goal is achieved. It should be noted that in some cases, complete deprescription may not be achieved and the patient may need to be on some maintenance therapy; whichever the case, the lifestyle changes usually result in better control, and in some cases emergence of hypoglycaemic episodes, requiring that some medications be withdrawn.
It would be most appropriate and safer to initiate therapeutic lifestyle changes first, before systematic and individualised withdrawal of the medications.
Unfortunately, there is no guideline, as at today, that guides the physicians in this regard. This article explores that factor to be considered, while deprescribing, in cases of revered type 2 diabetes.
Some have suggested deprescribing, in the same order that the medications were prescribed4; while this may work for some patients, it may not be suited for others. In the guideline for the pharmacological management of Type 2 DM, metformin is the first line, unless it is contraindicated; second line is dependent on the patient’s comorbidities.
Glucagon like peptide 1 receptor agonist (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i), have been shown to be cardio and reno-protective6,7; they are recommended as second line add-on to metformin, in patients with comorbid cardiac disease or renal complication of diabetes. For other groups of patients, any of the medications can be used as the second line therapy, after metformin.
In those individuals with comorbid renal and cardiac diseases, withholding metformin and leaving them on SGLT2i and GLP1RA may be more beneficial, even though they were added after metformin. Also, GLP-1RA would help maintain the patient’s weight loss, and may therefore be the last medication to be withdrawn, rather than metformin.
Therefore, I propose that the following factors should guide the deprescription in reversed Type 2 diabetes:
- Hypoglycaemia- Weight loss increases insulin sensitivity, with consequent increase in risk for hypoglycaemia. Also, the low calories and decrease in carbohydrate intake, or extended fasting increase the risk of hypoglycaemia.
Therefore, medications capable of causing hypoglycaemia, such as insulin and sulfonylureas may be the first medications to adjust and stop once the patient’s values start showing evidence of successful reversal. - Comorbidities – As noted above, the patient’s comorbidities should be considered. There is a good benefit of SGLT-2i in heart failure; the class of the medication is also beneficial in patients with ischaemic heart disease and decrease the progression of the renal disease in Type 2 diabetes, just as medications in the GLP1-RA class. Hence, one may need to live these medications behind, to maintain the reversed diabetes and give the patient the listed benefits.
- Maintaining the weight loss – GLP1-RA and SGLT-2i also have the benefit of weight loss; hence, they may be left as the last medication to be stopped, to help keep the patient’s weight low; especially, if the patient is struggling to maintain the weight he/she has lost.
- Medicare restrictions/cost – In Australia, Medicare restrictions in terms of the Pharmacological Benefit Scheme (PBS) rebates, makes it difficult to adopt some desired combinations of diabetes medications, or to use any other as monotherapy, instead of metformin or sulfonylurea.
For instance, Medicare would not reimburse for the use of GLP-1RA or SGLT-2i, as the last therapy, because the doctor decided to leave them behind, after withdrawing metformin, to help with the other comorbid conditions or to help with maintenance of low weight. These medications do not come cheap either, hence, this is a huge factor.
Reversing Type 2 diabetes comes with a challenge of deprescription; systematic and individualised approach should be adopted, to minimise harm and achieve a long-term remission. Regular review and monitoring are also needed in a patient whose medications have been completely or partially ceased, as relapse of the condition can occur at any time.
- Lean M E; Leslie W S; Barnes A C. Primary care-led Weight Management for Remission of Type 2 Diabetes (DiRECT): an Open-label, cluster-randomised trial. Lancet. 2018 Feb 10;39:541-551.
- McCombie L., Leslie W., Taylor R., Kennon B., Sattar N., Lean M.E.J. Beating type 2 diabetes into remission. 2017;358:j4030. doi: 10.1136/bmj.j4030.
- Isabelle Lemieux. Reversing Type 2 Diabetes: The Time for lifestyle Medicine Has Come! Nutrients, 2020 Jul; 12(7); 1974.
- Sarah J H; Victoria M G; Tamara L H; Shaminie J A. Reversing Type 2 Diabetes: A Narrative Review of the Evidence. Nutrients. 2019 Apr; 11(4): 766.
- Liam Davenport. Progress on T2D ‘Creates Need for De-prescribing Protocols’. Medscape News UK > DPC 2019.
- Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019;393:31–39.
- Asim A E, Noora A H, Israa Y E et al. Glucagon-like Peptide Receptor Agonists Cardio-protective Effects: An Umbrella Review. Curr Diabetes Rev. 2020;16(8):880-832.
This article has been written for the Australasian Society of Lifestyle Medicine (ASLM) by the documented original author. The views and opinions expressed in this article are solely those of the original author and do not necessarily represent the views and opinions of the ASLM or its Board.