FIGURE 41–6 Suggested algorithm for the treatment of type 2 diabetes. The seven main classes of agents are metformin, sulfonylureas (includes nateglinide, repaglinide), pioglitazone, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors, insulins. (α-Glucosidase inhibitors, colesevelam, pramlintide, and bromocriptine not included because of limited efficacy and significant adverse reactions). (Data from the consensus panel of the American Diabetes Association/ European Association for the Study of Diabetes, as described in Inzucchi SE et al: Diabetes Care 2012;35:1364.) hyperglycemia after a carbohydrate-rich meal (such as dinner), a short-acting secretagogue before that meal may suffice to control the glucose levels. Patients with severe insulin resistance may be candidates for pioglitazone. Patients who are very concerned about weight gain may benefit from a trial of a GLP-1 receptor agonist, a DPP-4 inhibitor, or an SGLT2 inhibitor, although the average weight loss with these medication is not great. If two agents are inadequate a third agent is added, although data regarding efficacy of such combined therapy are limited.
When the combination of oral agents and injectable GLP-1 receptor agonists fails to adequately control glucose levels, insulin therapy should be instituted. Various insulin regimens may be effective. Simply adding nighttime intermediateor long-acting insulin to the oral regimen may lead to improved fasting glucose levels and adequate control during the day. If daytime glucose levels are problematic, premixed insulins before breakfast and dinner may help. If such a regimen does not achieve adequate control or leads to unacceptable rates of hypoglycemia, a more intensive basal bolus insulin regimen (long-acting basal insulin) combined with rapid-acting analog before meals can be instituted. Metformin has been shown to be effective when combined with insulin therapy and should be continued. Pioglitazone can be used with insulin, but this combination is associated with more weight gain and peripheral and macular edema. Continuing with sulfonylureas, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors can be of benefit in selected patients. Cost, complexity, and risk for adverse events should be considered when deciding which drugs to continue once the patient starts on insulin therapy.
Acute Complications of Diabetes
A. Hypoglycemia
Hypoglycemic reactions are the most common complication of insulin therapy. It can also occur in any patient taking oral agents that stimulate insulin secretion (eg, sulfonylureas, meglitinide, d-phenylalanine analogs), particularly if the patient is elderly, has renal or liver disease, or is taking certain other medications that alter metabolism of the sulfonylureas (eg, phenylbutazone, sulfonamides, warfarin). It occurs more frequently with the use of long-acting sulfonylureas.
Rapid development of hypoglycemia in persons with intact hypoglycemic awareness causes signs of autonomic hyperactivity— both sympathetic (tachycardia, palpitations, sweating, tremulousness) and parasympathetic (nausea, hunger)—and may progress to convulsions and coma if untreated.