PracticeUpdate Diabetes Best of 2018

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Treatment in Type 1 and Type 2 Diabetes in Low-Resource Settings Annals of Internal Medicine Take-home message • This article presents five WHO recommendations for the intensification of treatment of type 2 diabetes and types of insulin to control type 1 and 2 diabetes in low-resource settings. Abstract DESCRIPTION The World Health Organization developed these guidelines to provide guidance on selection of medicines for treatment intensifica- tion in type 2 diabetes and on use of insulin (human or analogue) in type 1 and 2 diabetes. The target audience includes clinicians, policymakers, national diabetes programmanagers, and medicine procurement officers. The target population is adults with type 1 or 2 diabetes in low-resource settings in low- or high-income countries. The guidelines also apply to disadvantaged populations in high-income countries. METHODS The recommendations were formulated by a 12-member guide- line development group and are based on high-quality systematic reviews identified via a search of several bibliographic databases from 1 January 2007 to 1 March 2017. The GRADE (Grading of Recommendations Assess- ment, Development and Evaluation) system was used to assess the quality of the evidence and the strength of the recommendations. The guideline was peer-reviewed by 6 external reviewers. RECOMMENDATION 1 Give a sulfonylurea to patients with type 2 diabetes who do not achieve glycemic control with metformin alone or who have contraindications to metformin (strong recommendation, moderate-qual- ity evidence). RECOMMENDATION 2 Introduce human insulin treatment to patients with type 2 diabetes who do not achieve glycemic control with metformin and/ or a sulfonylurea (strong recommendation, very-low-quality evidence). RECOMMENDATION 3 If insulin is unsuitable, a dipeptidyl peptidase-4 (DPP-4) inhibitor, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, or a thiazoli- dinedione (TZD) may be added (weak recommendation, very-low-quality evidence). RECOMMENDATION 4 Use human insulin to manage blood glucose in adults with type 1 diabetes and in adults with type 2 diabetes for whom insulin is indicated (strong recommendation, low-quality evidence). RECOMMENDATION 5 Consider long-acting insulin analogues to manage blood glucose in adults with type 1 or type 2 diabetes who have frequent severe hypoglycemia with human insulin (weak recommendation, mod- erate-quality evidence for severe hypoglycemia). Medicines for Treatment Intensification in Type 2 Diabetes and Type of Insulin in Type 1 and Type 2 Diabetes in Low-Resource Settings: Synopsis of the World Health Organization Guidelines on Second- and Third-Line Medicines and Type of Insulin for the Control of Blood Glucose Levels in Nonpregnant Adults With Diabetes Mellitus. Ann. Intern. Med 2018 Sep 18;[EPub Ahead of Print], G Roglic, SL Norris. www.practiceupdate.com/c/73666 countries currently bear the brunt of the global burden of diabetes, and use of brand- name medications can rapidly deplete national and personal healthcare budgets. " " These guidelines are important and timely considering that low- and middle-income

COMMENT By Sylvia Kehlenbrink MD and Meredith Hawkins MD, MS T he current clinical guidelines by the World Health Organization (WHO) on optimizing glycemic control in non-pregnant adults with diabetes mellitus in low-re- source settings offers a pragmatic and cost-effective guide to decision-making in resource-constrained contexts. These guidelines are important and timely considering that low- and middle-income countries currently bear the brunt of the global burden of diabetes, and use of brand-name medications can rapidly deplete national and personal healthcare budgets. 1 Given their effectiveness and cost, the WHO guidelines recom- mend the addition of a sulfonylurea as second-line therapy to metformin. This is consistent with the recently released ADA/ EASD guidelines, which recommend the use of sulfonylureas or thiazolidinediones as second-line antihyperglycemic agents if cost is an overriding consideration, despite their preference for GLP-1 analogues or SGLT2 inhibitors in the presence of atherosclerotic cardiovascular disease. 2 Indeed, these newer antihyperglycemic agents can be up to 65 times more expen- sive than generic sulfonylureas and metformin. 3 Nonetheless, the benefits of HbA1c-lowering must be carefully weighed with the risk of hypoglycemia, which can lead to increased morbid- ity and mortality. Thus, the WHO guidelines suggest that newer agents be reserved as third-line agents for selected vulnera- ble populations, particularly when the use of insulin is difficult. Moreover, the WHO Expert Committee has repeatedly recom- mended against the addition of analogue insulins to the list of essential medicines, 4 concluding that their modest advan- tages did not justify the inclusion on the list, given their high cost. 5 Indeed, despite the cited “moderate quality evidence” for fewer severe hypoglycemic events with glargine, a recent report suggests that the use of basal insulin analogues in clin- ical practice settings may not be associated with reduced risk of hypoglycemia or improved glycemic control relative to NPH insulin. 6 Acknowledgements: The authors thank Dr. Jill Crandall, Chief of Endocrinology at Albert Einstein College of Medicine, for helpful comments. Disclosures: Sylvia Kehlenbrink serves as a consultant for Health Action International and the Medicines Patent Pool. References 1. International Diabetes Federation Diabetes Atlas 7th Edition: International Diabetes Federation; 2015. Available at: www.idf.org/e-library/ epidemiology-research/diabetes-atlas/13-diabetes-atlas-seventh-edition. html 2. Tucker ME. New ADA/EASD Guidance on Diabetes: Assess CV Status First. Available at: www.medscape.com/viewarticle/898697 . Accessed October 4, 2018. 3. Just a spoonful of medicine helps the sugar go down: Improving the management of type 2 diabetes: Alosa Health; 2016. Available at: http:// alosahealth.org/uploads/Diabetes_EvDoc_Final.pdf 4. WHO Model List of Essential Medicines. World Health Organization, 2017. Available at: www.who.int/medicines/publications/ essentialmedicines/20th_EML2017.pdf 5. The Selection and Use of Essential Medicines: Report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2017; 2017. Available at: http://apps.who.int/iris/bitstream/han dle/10665/259481/9789241210157-eng.pdf 6. Lipska KJ, Parker MM, Moffet HH, et al. Association of initiation of basal insulin analogs vs neutral protamine hagedorn insulin with hypoglycemia- related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA 2018;320(1):53-62.

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