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a second oral agent should be added. but some studies indicate that metformin plus another agent generally has better efficacy than other monotherapies or combination therapies. Modest restriction of saturated fats and simple sugars is also reasonable. the American College of Physicians (ACP) issued updated guidelines for the oral treatment of type 2 diabetes. diet modification has been the cornerstone of diabetes management. low-carbohydrate diets of various sorts. 232] These drugs allow for the use of combination oral therapy. Metformin is the drug of choice for initial monotherapy unless contraindicated. such as orlistat. However. Attempts to calibrate a precise macronutrient composition of the diet to control diabetes. although studies are ongoing. are generally not supported by the research. Therefore.[150] . some patients have remarkable short-term success with high-fat. Patients who are symptomatic at initial presentation with diabetes may require transient treatment with insulin to reduce glucose toxicity (which may reduce beta cell insulin secretion and worsen insulin resistance) or an insulin secretagogue to rapidly relieve symptoms such as polyuria and polydipsia.[149] Caloric restriction is of first importance. clinicians should add oral drug therapy. Medications that induce weight loss. Weight loss is more likely to control glycemia in patients with recent onset of the disease than in patients who are significantly insulinopenic. No combination therapy is recommended over another. often with improvement in glycemic control that was previously beyond the reach of medical therapy. may be effective in highly selected patients but are not generally indicated in the treatment of the average patient with type 2 diabetes mellitus.Medication Summary Pharmacologic therapy has changed dramatically in the last 10 years. the best diet is one consisting of the foods that they are currently eating.[233] The recommendations. published in the Annals of Internal Medicine. New drug classes and new drugs have become available for the treatment of type 2 diabetes. In 2012. include the following: • • • When diet. Traditionally. Also.[231. After that. the author always stresses weight management in general and is flexible regarding the precise diet that the patient consumes. while time-honored. exercise. and weight loss fail to improve hyperglycemia in patients with diabetes. the practitioner should advocate a diet using foods that are within the financial reach and cultural milieu of the patient. A weight loss strategy in children may help preserve insulin sensitivity. individual preference is reasonable. If metformin and lifestyle modifications fail to control hyperglycemia. Ectopic fat deposition in liver and elsewhere adversely impacts insulin sensitivity. Dietary Modifications For most patients.

A study by Larsen et al concluded a high-protein diet offers no superior long-term therapeutic beneficial effect compared with a high-carbohydrate diet in the treatment of type 2 diabetes mellitus.[155] Since there is no known treatment of nonalcoholic fatty liver disease. and atherogenic dyslipidemia. participants assigned to the Mediterranean-style diet had lost more weight and had demonstrated more improvement in some measures of glycemic control and coronary risk than had participants consuming the low-fat diet.[156] Trans -palmitoleate is principally derived from naturally occurring dairy and other ruminant trans -fats. Potential health benefits. [152] In a single-center.[153] Already attenuated glucose disposal is not worsened by postprandial circulating amino acid concentration. on hepatic steatosis in those with type 2 diabetes. increase in HDL cholesterol. recommendations to restrict dietary proteins in patients with type 2 diabetes seem unwarranted. need to be explored. After 4 years. 44% of patients in the Mediterranean-style diet group required antihyperglycemic drug therapy. Food-derived pro-oxidant advanced glycation end products may contribute to insulin resistance in clinical type 2 diabetes mellitus and may suppress protective mechanisms. In the Cardiovascular Health Study. and decrease in plasma triglycerides) in patients with type 2 diabetes mellitus.[154] A study by Lazo et al attested to the benefits of lifestyle intervention. Therefore. reduced blood pressure. Circulating trans -palmitoleate is associated with lower insulin resistance. Mediterranean-style diet compared with a low-fat diet in patients with newly diagnosed type 2 diabetes mellitus. a weight loss strategy might help prevent progression to serious liver damage.[157] . decreased HbA1c levels. phospholipid trans -palmitoleate levels were found to be associated with lower metabolic risk. Advanced glycation end product restriction may preserve native defenses and insulin sensitivity by maintaining a lower basal oxidative state. randomized trial. therefore.[151] Esposito et al reported greater benefit from a low-carbohydrate. which aimed at a minimum weight loss of 7%. Risk factor reduction was even greater with losses of 10-15% of body weight. compared with 70% of those in the low-fat diet group. incident of diabetes.Modest weight losses of 5-10% were associated with significant improvements in cardiovascular disease risk factors (ie. 215 overweight patients with newly diagnosed type 2 diabetes mellitus who had never been treated with antihyperglycemic drugs and whose HbA1c levels were less than 11% were assigned to either a Mediterranean-style diet (< 50% of daily calories from carbohydrates) or a low-fat diet (< 30% of daily calories from fat).

Many patients require multiple agents.[177] .[176] The addition of the ARB telmisartan to usual care in patients at high risk for CVD did not prevent incident diabetes or lead to regression of IFG or IGT. 173] The ADA suggests that the BP goal be below 130/80 mm Hg. diuretics. A study by Fogari et al found that.[172. angiotensin receptor blockers (ARB). beta blockers.Management of Hypertension The role of hypertension in increasing microvascular and macrovascular risk in patients with diabetes mellitus has been confirmed in the UKPDS and Hypertension Optimal Treatment (HOT) trials. According to the Veterans Affairs Diabetes Trial. a diastolic blood pressure of less than 70 mm Hg increases the risk of cardiovascular disease in patients with diabetes. the author prefers inhibitors of the renin-angiotensin system (ie. ARB) because of their proven renal protection effects in patients with diabetes. ACE inhibitors. Diuretics or calcium channel blockers frequently are useful as second and third agents. the angiotensin II receptor antagonist losartan provided greater attenuation of left ventricular hypertrophy in hypertensive patients with type 2 diabetes. In patients with greater than 1 g/d proteinuria and renal insufficiency. < 140 mm Hg). and calcium channel blockers are all considered acceptable initial therapy.[174] While ACE inhibitors. compared with amlodipine.[175] A study by Hermado et al showed that treatment with antihypertensive medications taken at bedtime provide better ambulatory blood pressure control as well as significant reduction in cardiovascular morbidity and mortality when compared with taking medications upon waking. even when systolic blood pressure is within the current guidelines (recommended range. a more aggressive therapeutic goal (ie. 125/75 mm Hg) is advocated.