New therapeutic agents, New thoughts

Dr Goh Su-Yen, Director, Diabetes Clinical Services, Singapore General Hospital

Many advances have been made in the pharmacotherapy of diabetes in recent years. The development of new classes of drugs like glucagon-like peptide 1 agonist, depeptidyl peptidase-4 inhibitors (DPP-4) and amylin agonists has increased treatment options for type 2 diabetes.

GIP is a 42–amino acid peptide produced in the duodenum in enteroendocrine K cells and is a physiological substrate for the enzyme dipeptidyl peptidase IV (DPP-IV) which clips and inactivates full-length GIP, thereby generating inactive GIP(3–42). GIP is secreted after nutrient ingestion, functions predominantly as an incretin, and enhances glucose-dependent insulin secretion.

GLP-1 is a naturally occurring peptide secreted by the small intestine, which stimulates insulin secretion. Exendin-4 is homologous, and synthetic exendin-4 (exenatide) is delivered by twice-daily subcutaneous injections. Exenatide suppresses glucagon secretion and slows gastric emptying, and seems to lower HbA1c by 0.5-1.0%.

The observation that both GIP and GLP-1 are rapidly degraded by the action of DPP-IV (93) has lead to the development of DPP-IV inhibitors. In animal models, DPP-IV inhibition improves glucose control, reduces A1C, and enhances insulin action but has no effect on satiety or body weight regulation Sitagliptin, an orally active, selective DPP-4 inhibitor, has been approved in 2006 by the FDA as monotherapy and as add-on therapy with metformin or thiazolinediones, and trial data shows an improvement in HbA1c of about 0.5-1.5% and seems to be more eff ective in patients with higher baseline HbA1c.

Islet amyloid polypeptide, or amylin, was originally identified as a major constituent of pancreatic amyloid deposits and subsequently shown to be a 37–amino acid peptide cosecreted together with insulin from islet ß-cells. The administration of exogenous amylin has been shown to result in inhibition of gastric emptying and glucagon secretion, leading to reduced food intake and weight loss.

Pramlintide is a synthetic analog of the beta-cell hormone amylin, and is administered via subcutaneous injection pre-meals, in conjunction with insulin therapy. HbA1c reduction in trials is about 0.5%.

Apart from pharmacological therapy, we believe that a lifestyle intervention program promoting weight management and increased physical activity should be part of the therapeutic plan for any patient with diabetes. In addition to the benefi cial effects of weight loss on glycemia, therapeutic lifestyle changes will also have a positive impact on cardiovascular risk factors like blood pressure and lipid profiles.

As all medical practitioners realise, patients often fail to reach glycemic goals despite our best efforts and polypharmacy. We sometimes overlook the importance of understanding factors behind patient adherence/compliance and it can be helpful to take a step back and put ourselves, literally, in the patient’s shoes.

One of the sessions at our recent Endocrinology Update was tailored after the Diabetes Education Study Group (DESG) of the European Association for the Study of Diabetes (EASD). The aim of the DESG is to improve the quality of life of the diabetic patient through the development and evaluation of educational programs designed to foster independence for the patient, improve the quality of metabolic control, emphasise the importance of prevention and early recognition of the disease, and encourage relevant research.

Over 50 GPs attended the diabetes sessions in our annual Endocrinology Update, and many participated gamely in the experiential learning. This included walking barefoot on sago and casuarina seeds scattered on the floor, simulating painful diabetic neuropathy, and attempting to perform activities of daily living like preparing a breakfast of coffee and bread while wearing waxed goggles to simulate impaired vision from diabetic retinopathy.

Our patients who have well-controlled and stable type 2 diabetes are now matched with General Practitioners who have completed the SingHealth "Delivering On Target" DOT program.

When the urgent metabolic issues are stabilised, the patients are offered an appointment within 3 months with a DOT-affiliated GP, and the GP is provided with the clinical summary and medication list within a week of the last consultation at the Diabetes Centre. A review date at the Diabetes Centre in 12 months, for the yearly screening of end-organ complications, is also offered. Similarly, we are working with the nurse educators from the Diabetic Society of Singapore to extend the reach of patient care and education in the community. We hope that these measures will facilitate the right-siting of care for patients with chronic diseases like diabetes.  

For more information on the Singhealth DOT program, contact Ms Hilda Ng, Assistant Manager – Clinical Networks, hilda.ng.s.h@singhealth.com.sg, DID 62367941.