Oral Antidiabetic Agents - Luzimar Teixeira

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388 Krentz & Bailey Table II. Main results for intensive (n = 80) vs conventional (n = 80) treatment of patients with type 2 diabetes mellitus and microalbuminuria. Mean follow-up was 7.8 years [8] Outcomes Intensive (%) Conventional (%) Adjusted HR (95% CI) RRR (95% CI) NNT (95% CI) Composite endpoint 24 44 0.47 (0.22, 0.74) 5 (3, 19) nephropathy 24 47 61% (13, 83) 4 (3, 14) retinopathy 52 71 58% (14, 79) 5 (3, 35) autonomic neuropathy 36 64 63% (21, 82) 4 (2, 9) HR = hazard ratio; NNT = number needed to treat; RRR = relative risk reduction. diabetes and are regarded as important modifiable physical activity. The objective is always to improve risk factors for atherosclerosis, the principal cause metabolic control through reductions in bodyweight of premature mortality. Thus, a combined mul- – obesity being present in the majority of patients – tifactorial therapeutic approach is required to max- and other lifestyle measures that help improve insuimise the impact of lifestyle and drug therapy on lin sensitivity. However, it is recognised that even if chronic micro- and macrovascular complications. diet and exercise advice is successfully implement- Since management of chronic vascular and neuro- ed, the majority of patients will require pharmacopathic complications accounts for the majority of logical therapy in the medium- to long term. Thus, health service spending for diabetes, such an ap- only 25% of patients in UKPDS maintained a HbA1c proach is likely to be cost effective. [7] The Steno-2 level
Oral Antidiabetic Agents 389 obese, sedentary middle-aged patients. Failure to diabetes. We consider both well established drugs respond rapidly (i.e. within a week or two) to an oral and recent additions to the armamentarium. For each agent in a patient thought to be complying with the class of agents we present an outline of the mode of dietary advice usually signals the need for early use action, pharmacokinetics, indications and contrainof insulin. If a partial response is observed, dose dications, efficacy, safety and tolerability, current escalation is followed by step-wise addition of com- place in management and future prospects, includplementary drugs (figure 1). Insulin is usually re- ing role in prevention of type 2 diabetes. We have served for patients: (i) who fail to respond adequate- grouped the drugs according to their principal mode ly to a combination of oral agents; (ii) in whom of action: (i) those that increase insulin secretion control deteriorates despite logical and adequate (insulin secretagogues); (ii) drugs delaying the rate drug combinations; or (iii) for whom safety and of digestion and absorption of carbohydrates (αefficacy considerations favour its use as the drug of glucosidase inhibitors); and (iii) those with direct choice, for example during pregnancy, or in patients effects on insulin-responsive tissues (insulin-senwith severe hepatic or renal impairment. [10] Several sitising agents). This sequence should not be taken classes of oral antidiabetic agents are currently to imply a hierarchy in terms of efficacy or merit. available, the range of options having enjoyed a The recognition that type 2 diabetes is usually a welcome expansion in recent years. However, the progressive disease implies that drug dosages will evidence base and clinical experience vary consider- need to be increased or therapy moved to another ably not only between classes but also between stage in the treatment algorithm. [2,4] drugs drawn from the same class. As a result, pre- While this article primarily reflects current pracscribing decisions often appear to be made on rather tice in the UK, we have endeavoured to provide a subjective grounds, such as familiarity with a particreview that acknowledges important differences in ular drug; this practice may help to explain notable prescribing in other countries. A word about moniregional differences in prescribing. toring: assessing the response to antidiabetic therapy In the remainder of this article we focus on involves periodic – generally 3- to 6-monthly – treatment of hyperglycaemia in patients with type 2 measurement of HbA 1c . This approach, which is Aim Diagnosis Procedure Diet, exercise, weight control and health education Relieve symptoms, improve glycaemic control, enhance quality of life Oral agent monotherapy: metformin, sulphonylurea, meglitinide, thiazolidinedione 1 , acarbose Oral agent combination therapy (using two different classes) Move to next stage if there is inadequate control of glycaemia or inadequate relief of symptoms Insulin or insulin plus an oral agent Fig. 1. An algorithm for the treatment of type 2 diabetes mellitus. The progressive hyperglycaemia in type 2 diabetes requires a steppedcare approach with treatment being modified and added over time. Rapid progression to the next stage is recommended if the glycaemic target is not achieved. Late introduction of combinations of oral antidiabetic agents is often a prelude to insulin treatment. 1 Note that in Europe, thiazolidinediones and nateglinide have limited licenses. The α-glucosidase inhibitor miglitol is also available in some countries (reproduced from Krentz and Bailey, [4] with permission from the Royal Society of Medicine Press). © 2005 Adis Data Information BV. All rights reserved. Drugs 2005; 65 (3)
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