Consideration of Individual Health Goals During Pharmacotherapy Intensification for Type 2 Diabetes: A Case Study
Optimal glycemic management for those living with type 2 diabetes (T2D) is essential to reduce the risk of macrovascular and microvascular complications.1 When diet and lifestyle measures are unable to adequately manage blood glucose levels, metformin is recommended as first-line pharmacotherapy and sulfonylureas were traditionally used as a second-line treatment.1, 2 Sulfonylureas are cheap and their long term safety and effectiveness have been established, however, the potential side effects of hypoglycaemia and weight gain due to hyperinsulinaemia can be problematic, particularly for the elderly and those who are overweight or obese.1, 3, 4 Despite this, sulfonylureas are commonly prescribed glucose lowering medications (GLMs) for management of T2D.3 Sulfonylureas work by triggering a glucose-independent release of insulin from pancreatic b cells, with studies suggesting mean weight gain after commencement ranges between 1.6 to 3.9kg.1, 3 Whilst concerns about weight gain and hypoglycaemia often cause delays to intensification of treatment, weight gain as an adverse side effect is not always considered a priority.4
The recently updated Australian Type 2 Diabetes Management Algorithm1, 5 provides a guide to assist selection of GLMs for management of T2D. Using the latest available evidence, the algorithm identifies mechanism of action, links to outcome data, contraindications, precautions, side effects, method of administration, cost and Pharmaceutical Benefits Scheme (PBS) accessibility, to assist clinicians to prescribe the most appropriate first, second, third and fourth-line GLMs. This case study demonstrates the importance of considering the health goals of the person with diabetes and the impact that choice of GLMs, in combination with diabetes self-management education (DSME) and medical nutrition therapy (MNT), has on an individual’s ability to reach their goals.
Details of person with diabetes
Mrs J, a 55 year old female, was referred to a rural health service outpatient dietetic service for MNT to assist in the management of T2D and obesity. Mrs J’s medical history included T2D diagnosed approximately 8 years ago, hypercholesterolaemia, osteoarthritis and angina. Her prescribed medications included, metformin 2 g daily and gliclazide MR 60 mg daily, in addition to two antihypertensive agents, a statin and glyceryl trinitrate (GTN). Mrs J had a body mass index (BMI) of 63.5kg/m2 and reported an increase in weight of 5kg over the previous 12months. Weight gain had occurred despite reported attempts to lose weight, including trial of very low-calorie meal replacements. Dietary assessment revealed a current intake of sugary drinks and discretionary foods, with occasional food binges due to increased perceived hunger. Mrs J reported doing gentle exercises twice weekly with a limited amount of incidental activity due to reduced mobility. Pathology showed fasting blood glucose 9.9mmol/L, glycated haemoglobin (HbA1c) 8.0% (64mmol/mol), total cholesterol 4.2mmol/L, high-density lipoprotein (HDL) 1.44mmol/L, low-density lipoprotein (LDL) 2.33mmol/L, triglycerides (TG) 1.0mmol/L, estimated glomerular filtration rate (eGFR) >90mL/min, urine albumin to creatinine ratio (ACR) 2.7mg/mmol and Liver Function Tests (LFTs) within normal limits.
Education or management provided
At initial assessment, Mrs J identified health goals including, weight loss, improved mobility and reduction in medication. The potential side effects of her current GLMs were discussed, and she reported being unaware of the potential side effects of her medications, although she had noted that her increased hunger and weight gain had coincided with the commencement of gliclazide MR (sulfonylurea). Following the initial appointment, correspondence was provided to Mrs J’s General Practitioner (GP), including recommendation to consider changing Mrs J’s second-line GLM (gliclazide) to an alternative option such as a Glucagon-like peptide-1 receptor agonist (GLP-1) that could assist Mrs J to achieve weight loss and improve glycaemia.
At review two months later, Mrs J had ceased gliclazide and commenced injections of Exenatide 5mcg twice daily, with continuation of metformin 2 g daily. Exenatide was increased to 10mcg twice daily within two months of commencement and then changed to the weekly formulation after a further four months, due to convenience (reduced frequency of injection and no timing limitations in relation to food).
At review consults over a period of two years, DSME and MNT was provided to assist Mrs J to achieve her health goals. Topics covered included self-monitoring of blood glucose levels, diabetes-related complications, the relationship between diet, lifestyle and blood glucose levels, glycaemic index, food portion sizes, healthier drink options, healthy dietary fats and the benefits of physical activity. Mrs J reported a significant reduction in appetite and oral intake, with positive dietary changes made. At 11months, Mrs J’s BMI decreased to 49.6kg/m2 (weight loss of 32.5kg) and was maintained for approximately 10 months before increasing to 52.3kg/m2 at 23 months (sustained weight loss of 26kg). Over time, Mrs J reported increased activity levels with improved mobility, and she was able to return to work, gardening and walking four times per week.
Unfortunately, at around 18months, Mrs J reported a reduction in activity levels due to injury and family crisis. Despite this, improvement in glycaemic management was maintained (HbA1c 6.2% (44mmol/L) at 5 months, 5.4% (36mmol/L) at 14months and 5.5% (37mmol/L) at 18months post medication change). Other pathology results at 18months showed fasting BGL 6.1mmol/L (↓3.8mmol/L), total cholesterol 5.5mmol/L (↑ 1.3mmol/L), HDL 1.56mmol/L (↑ 0.12mmol/L), LDL 3.3mmol/L (↑ 0.97mmol/L), TG 1.3mmol/L (↑ 0.3mmol/L), eGFR >90 (no change), and LFTs within normal limits (no change). The reason for the increase to total cholesterol, LDL and TG remains unclear. Mrs J’s medications had also changed at this time, with metformin dose being decreased to 500mg daily and antihypertensives reduced from two agents to one. Information about the frequency of angina episodes and use of GTN was unavailable, therefore it could not be determined if there were any improvements.
With advances in diabetes treatments and evolving evidence, choice of pharmacotherapy requires consideration of many factors, including cardiovascular disease risk, renal function, age, hypoglycaemia risk and cost.1, 5 Whilst these are important clinical considerations, the individual’s health goals also need to be discussed and reflected on to ensure the most suitable medication is recommended and allow individuals to make informed decisions. With increased weight accounting for 80-85% of the risk for development of T2D, a significant proportion of those with T2D are overweight or obese.4 Studies show that modest weight loss of between 5 to 10% reduces complications associated with diabetes, therefore weight should be a factor for consideration when intensification of diabetes treatment is required.4
A GLP-1 was recommended as a treatment option in this case as this class of medications can assist with weight loss. GLP-1 medications work by stimulating beta-cell insulin release in a glucose dependent manner, slowing gastric emptying and increasing satiety.5, 6, 7 Studies show weight loss associated with commencement of a GLP-1 agent ranges between 2.3 and 4.4kg, (with greater weight loss occurring with a higher BMI) and HbA1c reduction of around 1.1%.6, 7 At time of Mrs J’s treatment, Dulaglutide was not yet subsidised under the PBS, however, compared with Exenatide it has been associated with reduced site reactions (pruritus, erythema, nodules & pain) and the pen device is easy to administer.8
It is difficult to determine whether change to medication or DSME and MNT had the greatest impacts on the outcomes in this case. Whilst a recent study evaluating the impact of DSME and MNT in T2D reported statistically significant improvements in weight, BMI and HbA1c with provision of MNT and DSME alone, greatest improvements in HbA1c were reported for those taking GLMs in combination with MNT and DSME.9 This suggests the impact of MNT, DSME and GLMs are additive.
In this case, Mrs J made significant progress towards achieving her health goals through a combination of changes to GLMs, DSME and MNT. Over a two-year period, Mrs J’s HbA1c improved by 2.5% (almost one third reduction in HbA1c), paralleled with an overall weight loss of 26kg (17.8% reduction in weight), resulting in a reduction in the number of medications prescribed. Undoubtedly, this has greatly reduced the health risks and complications associated with obesity and diabetes for Mrs J.
When intensifying pharmacotherapy to improve glycaemic management for people living with T2D, it is important that all potential side effects and the individual’s health goals are considered and discussed. Obesity in T2D should be considered a contraindication to commencing medications associated with weight gain, unless the risks are outweighed by the expected benefits or there are no suitable alternatives.
The author would like to acknowledge Achamma Joseph, APD CDE for assistance with reading and editing the case study.
Gunton JE, Cheung NW, Davis TM, Zoungas S, Calagiuri S. A new blood glucose management algorithm for type 2 diabetes. Med J Aust [internet]. 2014 Dec [cited 07/01/2020];201(11): 650-53. Available from: https://www.mja.com.au/journal/2014/201/11/new-blood-glucose-management-algorithm-type-2-diabetes-position-statement DOI: 10.5694/mja14.011872.
Farah D, Leme GM, Eliaschewitz FG, Fonseca MC. A safety and tolerability profile comparison between dipeptidyl peptidase-4 inhibitors and sulfonylureas in diabetic patients: A systematic review and meta-analysis. Diabetes Res Clin Pract. [internet]. 2019 Jan [cited 07/01/2020];149:47-63. Available from: https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(18)31507-9/fulltext DOI: https://doi.org/10.1016/j.diabres.2019.01.025
Khunti K, Chatterjee S, Gerstein HC, Zoungas S, Davies MJ. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol [internet]. 2018 Feb [cited 07/01/2020];6(10):821-32. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30025-1 DOI: doi: 10.1016/S2213-8587(18)30025-14.
Chen V and Kashyap SR. Weight considerations in Pharmacotherapy for type 2 diabetes. J Obes [internet] 2011 Jul [cited 12/01/2020]; 11:1-9. Available from: http://downloads.hindawi.com/journals/jobe/2011/984245.pdf DOI: 10.1155/2011/9842455.
Australian Diabetes Society (ADS). Australian Blood Glucose Treatment Algorithm for type 2 diabetes [internet]. ADS; 2016 [cited 12/01/2020]. Available from: http://t2d.diabetessociety.com.au/plan/
Dar S, Tahrani AA, Piya MK. The role of GLP-1 receptor agonists as weight loss agents in patients with and without type 2 diabetes. Practical Diabetes [internet]. 2015 Sep [cited 12/01/2020]; 32(8): 297-300b. Available from: https://www.practicaldiabetes.com/wp-content/uploads/sites/29/2016/04/The-role-of-GLP-1-receptor-agonists-as-weight-loss-agents-in-patients-with-and-without-type-2-diabetes.pdf
Hollander P, Anti-diabetes and anti-obesity medications: Effects on weight in people with diabetes. Diabetes Spectrum [internet]. 2007 Jul [cited 12/01/2020]; 20(3):159-65. Available from: https://spectrum.diabetesjournals.org/content/20/3/159.full-text.pdf
Diabetes Queensland. Introducing Trulicity (Dulaglutide) [internet]. Diabetes Queensland; 2018 [cited 20/02/2020]. Available from: https://www.diabetesqld.org.au/media-centre/2018/june/introducing-trulicity-dulaglutide.aspx
Marincic PZ et al. Diabetes self-management education and medical nutrition therapy: a multisite study documenting the efficacy of Registered Dietitian Nutritionist interventions in the management of glycemic control and diabetic dyslipidemia through retrospective chart review. J Acad Nutr Diet [internet]. 2018 Sep [cited 12/01/20]; 119(3);449-63. Available: https://doi.org/10.1016/j.jand.2018.06.303