Benefits and Risks of Transfer from Oral Agents to Insulin in Type 2 Diabetes Mellitus

Abstract

The treatment of type 2 diabetes mellitus remains controversial. Since most patients are overweight or obese, regimens based on dietary modification and increased physical exercise are logical and safe treatment approaches. However, the long term impact of these interventions is frequently disappointing and pharmacotherapy is therefore required in the majority of patients. Oral antidiabetic agents, principally the sulphonylureas and biguanides, are often only partially effective, even in combination. Insulin is the treatment of choice for certain clinical situations, for example, pregnancy. Often insulin will be a temporary measure. Safety considerations will also point to the preferential use of insulin in other circumstances, for example, in patients with pronounced renal impairment. In addition, a significant proportion of patients with type 2 diabetes mellitus will ultimately require insulin therapy in the long term because of failure of oral agents to provide adequate glycaemic control (i.e. secondary failure). Reservations about insulin therapy in patients with type 2 diabetes mellitus, particularly elderly patients with cardiovascular complications, include hypoglycaemia and bodyweight gain. However, severe hypoglycaemia occurs with considerably lower frequency than in patients with type 1 diabetes mellitus. To date, no clear evidence has emerged implicating exogenous insulin therapy in the promotion of cardiovascular disease. On the contrary, recent clinical and experimental studies suggest anti-atherogenic effects. Insulin therapy can be successful in type 2 diabetes mellitus if patients are carefully selected. Twice daily isophane (neutral protamine Hagedom; NPH) or pre-mixed insulin is used routinely in many centres. The role of combinations of insulin and oral agents remains an area of controversy. Combined therapy with sulphonylureas may be more expensive and clear clinical advantages have not been consistently demonstrated. Bodyweight gain may be lessened by the concomitant use of metformin and troglitazone may improve glycaemic control in obese patients. Procrastination about transfer to insulin is not uncommon. Patient acceptance may be facilitated by a positive attitude from the diabetes care team and discussion of the possibility at a relatively early stage. Adequate support from a multidisciplinary team is important for safe and effective insulin therapy. Even so, in the long term, attainment of glycaemic targets may prove difficult to sustain with present therapeutic strategies.

Effect of Duodenal–Jejunal Exclusion in a Non-obese Animal Model of Type 2 Diabetes

“…33 Furthermore, insulin therapy has limited long-term efficacy in type 2 diabetes because of poor patient compliance to the regimen complexity and fear of weight gain and reduced quality of life. 34 In addition, glycemic control tends to deteriorate over time even after treatment. 35 The results of the Costs of Diabetes in Europe-Type 2 indicated that most patients with type 2 diabetes have either poor or borderline glycemic control.…”

“…First, long-term glycemic control would not be impaired by a patient's lack of compliance as it happens for diets, exercise, or complex medical regimens. 34 Moreover, a surgical treatment of type 2 diabetes could decrease the overall economic burden on health care systems by avoiding the costs of a life-long medical therapy. Tight blood glucose control is indeed associated with increased cost of intensive medical management 39 and therefore surgery might be a cost-effective option for the management of type 2 diabetes.…”

Development of techniques for gastrojejunal bypass surgery in obese mice

“…So far, no pharmacological cure for type 2 diabetes exists, but recent findings suggesting long-term improvement in glucose homeostasis in obese patients who underwent bariatric surgery may provide new opportunities in the fight against this global disease. [1][2][3] Buchwald et al, 4 in a meta-analysis of 22,094 patients with type 2 diabetes, who underwent gastrointestinal bypass for morbid obesity, showed that greater than 80% had complete resolution of their diabetes postoperatively. In addition, all gastrointestinal bypass procedures, such as the Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD), demonstrate a great improvement in glucose tolerance, with reported rates of 83.7-98.9% having complete resolution of diabetes.…”

Prevention of Cardiovascular Complications of the Metabolic Syndrome: Focus on Pharmacotherapy

“…50 The risks and benefits of insulin therapy in patients with type 2 diabetes has been a topic of much debate. 51 Concerns have been expressed that by inducing hyperinsulinemia, insulin therapy might be detrimental to vascular health. However, the effects of insulin on atherothrombosis have been clouded by studies that have sometimes had limited relevance for human pathophysiology 52 and that have failed to make the crucial distinction between hyperinsulinemia and deficient cellular insulin action.…”

“…The failure of insulin therapy to provide unequivocal evidence of protection against macrovascular disease in the UKPDS should not detract from more enthusiastic use of insulin. 51 There are sound theoretical reasons to favor insulin therapy in patients in whom insulin-or insulin action-is deficient. In addition to an adverse profile of metabolic risk factors, defective cellular insulin action may also have direct implications for the vasculature.…”