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Actively targeting weight loss for glycaemic control in type 2 diabetes

12 Mar 2025
GP Connect News

GP Connect Clinical Feature by Dr Gregory Ong MBBS (WA), PhD (Monash), FRACP, Principal Endocrinologist – Diabetes Connect (Diabetes WA)

Obesity is formally defined as a disease state of excess adiposity posing a threat to health.1 An increasingly prevalent problem for our community, it not only impacts on individuals but also on society through significant direct health care costs and indirectly through loss of productivity.2 Obesity can cause diverse complications including arthritis, sleep apnoea, asthma, gastro-oesophageal reflux, infertility and increase the risk of cancers.3 The adverse metabolic and cardiovascular risk state, including onset of type 2 diabetes (T2DM), contributes to premature mortality.4 While it is common for “lifestyle” measures to be mentioned in guidelines as a general part of holistic diabetes care, weight management has historically not been given as much visibility as other aspects of diabetes management, such as pharmacotherapy. There is also an inconsistent approach to accepting obesity as a “disease” rather than a risk factor, which seems trivial but affects the approach of policymakers and clinicians.5

Identifying benefits of weight management for patients with T2DM

Glycaemic control is challenging, despite availability of many classes of potent agents and better concepts of care over time.6 Obesity has plausible mechanistic and epidemiological links to hyperglycaemia. Hence, it follows that weight management should modify the course of T2DM for patients who are overweight or obese. There is good evidence that weight loss can achieve a state of prolonged normoglycaemia without needing glucose lowering medications. It does not matter if this is done through behavioural modification, total meal replacement with specially formulated very low energy diets such as Optifast®, using weight loss specific medications, or through “bariatric” or “metabolic surgery”.7

There is a large variation in the degree of weight loss that can be achieved with any modality. This reflects the complex nature of weight management and the nexus between physiology and psychology in driving appetite and metabolism. As a rule, success in achieving normoglycaemia depends on greater magnitude of weight loss, particularly more than 10-15 per cent of baseline.7 Unfortunately, there is only a narrow window to achieve drug-free remission from hyperglycaemia. Even with substantial weight loss, patients with longer duration of T2DM, or those who are already on insulin may not succeed.7,8 However, this should not dampen enthusiasm for weight loss, as partial glycaemic responses and improvements to other morbidities and cardiovascular risk are still worthwhile.

Preferencing evidence-based treatments with cardiovascular benefits

Only some treatments have robust evidence for reducing hard cardiovascular (CV) endpoints such as heart attacks and stroke. This is not the same as improving risk factors such as blood pressure and lipids, which ultimately are only surrogate markers.

  • High quality randomized controlled trial evidence exists for GLP-1 receptor agonists (GLP-1RA) such as liraglutide, semaglutide and dulaglutide9 and SGLT2 inhibitors.10
  • Meta-analyses and observational studies suggest that bariatric surgery is also useful.11,12
  • Trials looking at phentermine with topiramate, orlistat, naltrexone/bupropion (Contrave) and very low energy diets have either not been statistically powered or did not specifically investigate CV events or mortality.13
  • Some effective weight loss agents, such as sibutramine, have been withdrawn due to worsening CV risk.13

Until more robust proof appears, it is logical to preference options with clear CV benefits for both diabetes and weight management, such as GLP-1RA – an approach recommended by the American Diabetes Association.14

Integrating weight management into holistic T2DM care

Any pharmacotherapy must be supported by a holistic approach including behavioural modification, review of existing morbidities and medications that contribute to weight gain, and periodic reappraisal to ensure targets are met and weight regain is avoided. Weight regain can occur despite bariatric surgery, and especially when a successful non-surgical approach is withdrawn.15,16 The in-built biological defence of weight is difficult to overcome through personal efforts, so it is important to openly discuss the potential for regain, the need for long term supervision and ongoing or repeat interventions.17

Weight management has now received greater prominence, with a dedicated section in the updated RACGP Management of type 2 diabetes handbook for general practice. Discuss weight management with patients as a core and early component of holistic T2DM care. Achieving weight goals with an evidence-based approach will alter the course of disease, and makes it more likely that all the usual diabetes metrics including quantity and quality of life can be met.

Further support for GPs

The Diabetes Connect program delivered by Diabetes WA supports primary care in regional WA by connecting GPs to direct phone advice, across all types of diabetes, from the Diabetes Connect Endocrinologist. For in-depth review of more complex cases a multidisciplinary case conference can be booked. To pre-book a call with an endocrinologist or to book a multidisciplinary case conference, call 9436 6270 or visit Diabetes Connect for Country WA.

Additional guidance is available at Clinician Assist WA, including:

 

References:

  1. Obesity and overweight
  2. Lee CM, Colagiuri R, Magliano DJ, et al. The cost of diabetes in adults in Australia. Diabetes Res Clin Pract. 2013;99(3):385-390
  3. Pi-Sunyer, X. The Medical Risks of Obesity. Postgraduate Medicine. 2009;121(6), 21–33.
  4. Chandrasekaran P, Weiskirchen R. The Role of Obesity in Type 2 Diabetes Mellitus-An Overview. Int J Mo0l Sci. 2024;25(3):1882
  5. Luli M, Yeo G, Farrell E, et al. The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference. EClinicalMedicine. 2023;58:101962
  6. Xiang AS, Szwarcbard N, Gasevic D, et al. Trends in glycaemic control and drug use in males and females with type 2 diabetes: Results of the Australian National Diabetes Audit from 2013 to 2019. Diabetes Obes Metab. 2021;23(12):2603-2613.
  7. Ko JH, Kim TN. Type 2 Diabetes Remission with Significant Weight Loss: Definition and Evidence-Based Interventions. J Obes Metab Syndr. 2022;31(2):123-133.
  8. DIRECT-AUS study presented at the ADS/ADEA Joint Symposium on Nutrition and Diabetes Remission. Proceedings of the Australian Diabetes Congress 2024.
  9. Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes. Circulation. 2022;146(24):1882-1894
  10. Toyama T, Neuen BL, Jun M, et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis. Diabetes Obes Metab. 2019;21(5):1237-1250
  11. Sutanto A, Wungu CDK, Susilo H, Sutanto H. Reduction of Major Adverse Cardiovascular Events (MACE) after Bariatric Surgery in Patients with Obesity and Cardiovascular Diseases: A Systematic Review and Meta-Analysis. Nutrients. 2021;13(10):3568
  12. Cohen R, Sforza NS, Clemente RG. Impact of Metabolic Surgery on Type 2 Diabetes Mellitus, Cardiovascular Risk Factors, and Mortality: A Review. Curr Hypertens Rev. 2021;17(2):159-169
  13. Alobaida M, Alrumayh A, Oguntade AS, Al-Amodi F, Bwalya M. Cardiovascular Safety and Superiority of Anti-Obesity Medications. Diabetes Metab Syndr Obes. 2021;14:3199-3208.
  14. American Diabetes Association Professional Practice Committee. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes–2025. Diabetes Care 2025;48(Suppl. 1):S167–S180
  15. Lean ME, Leslie WS, Barnes AC, et al. 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study [published correction appears in Lancet Diabetes Endocrinol. 2024 Jun;12(6):e17.
  16. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564
  17. Bessesen DH, Van Gaal LF. Progress and challenges in anti-obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018;6(3):237-248

 

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