Initial management of blood glucose in adults with type 2 diabetes mellitus
- David K McCulloch, MD
David K McCulloch, MD
- Washington Permanente Medical Group
Treatment of patients with type 2 diabetes mellitus includes education, evaluation for microvascular and macrovascular complications, attempts to achieve near-normal glycemia, minimization of cardiovascular and other long-term risk factors, and avoidance of drugs that can aggravate abnormalities of insulin or lipid metabolism. All of these treatments need to be tempered based on individual factors, such as age, life expectancy, and comorbidities. Although several studies have noted remissions of type 2 diabetes mellitus that may last several years, most patients require continuous treatment in order to maintain normal or near-normal glycemia. Treatments to achieve normoglycemia focus on increasing insulin availability (either through direct insulin administration or through agents that promote insulin secretion), improving sensitivity to insulin, delaying the delivery and absorption of carbohydrate from the gastrointestinal tract, or increasing urinary glucose excretion.
Methods used to control blood glucose in patients with newly diagnosed type 2 diabetes are reviewed here. Further management of persistent hyperglycemia and other therapeutic issues, such as the frequency of monitoring and evaluation for microvascular and macrovascular complications, are discussed separately. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus" and "Overview of medical care in adults with diabetes mellitus".)
Degree of glycemic control — Improved glycemic control improves the risk of microvascular complications in patients with type 2 diabetes (figure 1) . Every 1 percent drop in glycated hemoglobin (A1C) is associated with improved outcomes with no threshold effect. To date, only one randomized clinical trial has demonstrated a beneficial effect of intensive therapy on macrovascular outcomes in type 2 diabetes , with several trials not supporting a beneficial effect [3,4] and one trial suggesting harm . A reasonable goal of therapy might be an A1C value of ≤7.0 percent (53.0 mmol/mol) (calculator 1) for most patients. However, target A1C goals in patients with type 2 diabetes should be tailored to the individual, balancing the improvement in microvascular complications with the risk of hypoglycemia. Glycemic targets are generally set somewhat higher for older adult patients and those with comorbidities or a limited life expectancy and little likelihood of benefit from intensive therapy. Glycemic goals are discussed in more detail separately. (See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Glycemic targets' and "Overview of medical care in adults with diabetes mellitus", section on 'Glycemic control' and "Treatment of type 2 diabetes mellitus in the older patient", section on 'Glycemic targets'.)
Cardiovascular risk factor management — In addition to glycemic control, vigorous cardiac risk reduction (smoking cessation, aspirin, blood pressure control, reduction in serum lipids, diet, and exercise) should be a top priority for all patients with type 2 diabetes. However, in spite of evidence that aggressive risk factor reduction lowers the risk of both micro- and macrovascular complications in patients with diabetes, many patients do not achieve recommended goals for A1C, blood pressure control, and management of dyslipidemia. (See "Overview of medical care in adults with diabetes mellitus" and "Treatment of hypertension in patients with diabetes mellitus" and "Treatment of lipids (including hypercholesterolemia) in primary prevention" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention".)
Patients with newly diagnosed diabetes should participate in a comprehensive diabetes self-management education program, which includes instruction on nutrition, physical activity, optimizing metabolic control, and preventing complications. In clinical trials comparing diabetes education with usual care, there was a small but statistically significant reduction in A1C in patients receiving the diabetes education intervention . There was no difference in quality of life. In two meta-analyses, use of mobile phone interventions for diabetes education was successful in significantly reducing A1C (-0.5 percentage points) [7,8].
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837.
- Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359:1577.
- Look AHEAD Research Group, Wing RR, Bolin P, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369:145.
- ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358:2560.
- Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358:2545.
- Pal K, Eastwood SV, Michie S, et al. Computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2013; :CD008776.
- Saffari M, Ghanizadeh G, Koenig HG. Health education via mobile text messaging for glycemic control in adults with type 2 diabetes: a systematic review and meta-analysis. Prim Care Diabetes 2014; 8:275.
- Liang X, Wang Q, Yang X, et al. Effect of mobile phone intervention for diabetes on glycaemic control: a meta-analysis. Diabet Med 2011; 28:455.
- Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1985; 61:917.
- Wing RR, Blair EH, Bononi P, et al. Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care 1994; 17:30.
- Niskanen LK, Uusitupa MI, Sarlund H, et al. Five-year follow-up study on plasma insulin levels in newly diagnosed NIDDM patients and nondiabetic subjects. Diabetes Care 1990; 13:41.
- Norris SL, Zhang X, Avenell A, et al. Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis. Am J Med 2004; 117:762.
- United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 1995; 310:83.
- Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2006; 29:1963.
- Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011; 305:1790.
- Jeon CY, Lokken RP, Hu FB, van Dam RM. Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 2007; 30:744.
- Egan AM, Mahmood WA, Fenton R, et al. Barriers to exercise in obese patients with type 2 diabetes. QJM 2013; 106:635.
- Pillay J, Armstrong MJ, Butalia S, et al. Behavioral Programs for Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-analysis. Ann Intern Med 2015; 163:848.
- Look AHEAD Research Group, Pi-Sunyer X, Blackburn G, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007; 30:1374.
- Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med 2010; 170:1566.
- Gregg EW, Chen H, Wagenknecht LE, et al. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 2012; 308:2489.
- Jakicic JM, Egan CM, Fabricatore AN, et al. Four-year change in cardiorespiratory fitness and influence on glycemic control in adults with type 2 diabetes in a randomized trial: the Look AHEAD Trial. Diabetes Care 2013; 36:1297.
- Kuna ST, Reboussin DM, Borradaile KE, et al. Long-term effect of weight loss on obstructive sleep apnea severity in obese patients with type 2 diabetes. Sleep 2013; 36:641.
- Wing RR, Bond DS, Gendrano IN 3rd, et al. Effect of intensive lifestyle intervention on sexual dysfunction in women with type 2 diabetes: results from an ancillary Look AHEAD study. Diabetes Care 2013; 36:2937.
- http://www.diabetes.org/for-media/2013/sci-sessions-look-ahead.html (Accessed on July 18, 2013).
- Look AHEAD Research Group. Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol 2014; 2:801.
- Arterburn DE, O'Connor PJ. A look ahead at the future of diabetes prevention and treatment. JAMA 2012; 308:2517.
- Surwit RS, van Tilburg MA, Zucker N, et al. Stress management improves long-term glycemic control in type 2 diabetes. Diabetes Care 2002; 25:30.
- Ismail K, Winkley K, Rabe-Hesketh S. Systematic review and meta-analysis of randomised controlled trials of psychological interventions to improve glycaemic control in patients with type 2 diabetes. Lancet 2004; 363:1589.
- Safren SA, Gonzalez JS, Wexler DJ, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with uncontrolled type 2 diabetes. Diabetes Care 2014; 37:625.
- Williams JW Jr, Katon W, Lin EH, et al. The effectiveness of depression care management on diabetes-related outcomes in older patients. Ann Intern Med 2004; 140:1015.
- Colagiuri S, Cull CA, Holman RR, UKPDS Group. Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes?: U.K. prospective diabetes study 61. Diabetes Care 2002; 25:1410.
- Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy. Update regarding the thiazolidinediones. Diabetologia 2008; 51:8.
- Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38:140.
- Desai NR, Shrank WH, Fischer MA, et al. Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications. Am J Med 2012; 125:302.e1.
- Davidson MB. Successful treatment of markedly symptomatic patients with type II diabetes mellitus using high doses of sulfonylurea agents. West J Med 1992; 157:199.
- https://effectivehealthcare.ahrq.gov/ehc/products/607/2215/diabetes-update-2016-report.pdf (Accessed on April 21, 2016).
- Maruthur NM, Tseng E, Hutfless S, et al. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 164:740.
- Karagiannis T, Paschos P, Paletas K, et al. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ 2012; 344:e1369.
- Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. JAMA 2016; 316:313.
- Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355:2427.
- Nathan DM. Thiazolidinediones for initial treatment of type 2 diabetes? N Engl J Med 2006; 355:2477.
- Hong J, Zhang Y, Lai S, et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 2013; 36:1304.
- Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med 2009; 169:616.
- Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32:193.
- Qaseem A, Barry MJ, Humphrey LL, et al. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med 2017.
- American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care 2017; 40:S64.
- TREATMENT GOALS
- Degree of glycemic control
- Cardiovascular risk factor management
- DIABETES EDUCATION
- Weight reduction
- - Diet
- - Pharmacologic therapy
- - Surgical therapy
- Intensive lifestyle modification
- Psychological interventions
- INITIAL PHARMACOLOGIC THERAPY
- When to start
- Choice of initial therapy
- - Asymptomatic
- A1C at (<7.6 percent) or close to (>0.5 to 1.5 percent above, eg, 7.6 to 8.5 percent) treatment goal
- A1C relatively far from goal (eg, 8.5 to 9.5 percent)
- Contraindications to metformin
- - Symptomatic or severe hyperglycemia
- - Difficult to distinguish type 1 from type 2
- Glycemic efficacy
- Cardiovascular outcomes
- PERSISTENT HYPERGLYCEMIA
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS