- Diagnosis and Classification of Diabetes
- Initial Assessment and Criteria for Specialist Referral
- Glycaemic Control in Type 2 Diabetes - Oral Hypoglycaemic Agents
- Indications for Insulin in Type 2 Diabetes
- Hypertension
- Dyslipidaemia
- Aspirin Therapy in Diabetes
- Retinopathy
- Nephropathy
- Neuropathy and Foot Ulcers
- Sexual Dysfunction in Men
- Diabetes in Pregnancy and Pre-conception Guidance
3. Glycaemic Control in Type 2 Diabetes - Oral Hypoglycaemic Agents
Measurement of haemoglobin A1c (HbA1c) provides a better estimate of chronic glycaemic control, particularly in type 1 diabetes, than measurements of fasting blood glucose. However, in type 2 diabetes, the correlation between fasting blood glucose and HbA1c values is reasonably good. Furthermore, by measuring fasting blood glucose, glycaemic control can be directly monitored by the patient, thereby allowing immediate feedback about the efficacy of therapy. It is recommended that patients be taught self blood sugar monitoring where possible. Some readings should also be obtained after meals and at other times during the day, and when hypoglycaemia is suspected.
The optimal level of glycaemic control in patients with type 2 diabetes is becoming clear. The Diabetes Control and Complications Trial demonstrated that achieving near normal blood glucose concentrations markedly reduces the risk of microvascular complications in type 1 diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) suggests that the same relationship applies to patients with type 2 diabetes: therapy with oral hypoglycaemic drugs or insulin (mean HbA1c value of 7.0%) resulted in a decreased risk of microvascular complications compared to therapy with diet (mean HbA1c value 7.9%). Sub-analysis of the UKPDS revealed no evidence of a threshold effect of HbA1c; a 1% reduction in HbA1c was associated with a 35% reduction in microvascular endpoints, an 18% reduction in myocardial infarction, and a 17% reduction in all-cause mortality.
It is recommended that the goal of therapy is HbA1c value of =7.0% for most patients (using an assay in which the upper limit of normal is 6.0%). The goal should be set somewhat higher for older patients and those with a limited life expectancy.
Diet, weight reduction, and exercise can all be used to improve glycaemic control.
Diet – Dietary modification can improve many aspects of type 2 diabetes, including obesity, hypertension, and insulin release and responsiveness. The improvement in glycaemic control is related both to the degree of caloric restriction and weight reduction. The likelihood of a successful response to diet is determined in large part by the initial fasting blood glucose. In the UKPDS, the degree of weight loss required to normalise the fasting blood glucose was 10 kg (16% of initial body weight) if the initial value was 6-8mmol/L versus 22 kg (35%) if the initial value was 12-14mmol/L.
Exercise – Regular exercise is beneficial in type 2 diabetes. It leads to improved glycaemic control due to increased responsiveness to insulin; it can also delay the progression of impaired glucose tolerance to overt diabetes. These effects are directly due to exercise but concurrent weight reduction can play a contributory role.
Choices For Initial Drug Therapy Of Hyperglycaemia
- Please also refer to NICE Guideline G: Management of Type 2 Diabetes - blood glucose
Metformin – This acts by a poorly understood mechanism to increase peripheral sensitivity to insulin. In people who are overweight (BMI >27Kg/m2), metformin should normally be used as the first-line glucose lowering therapy in those inadequately controlled on lifestyle management alone. Metformin is available as 500 and 850 mg tablets, which should be taken with meals; it should not be given to patients who have renal (creatinine >150µmol/L), hepatic disease, cardiac failure or drink excess alcohol. It dose not cause hypoglycaemia. Begin with 250mg or 500 mg once daily with the evening meal and, if tolerated, add a second 500mg dose with breakfast after 7 days. The dose can be increased slowly (one tablet every one to two weeks) as necessary to a maximum of 3g/day. Approximately 10% of patients are unable to tolerate metformin because of GI side effects.
Sulphonylureas – These act on the K+ channel of the ß cell, sensitising them to the action of glucose, leading to an increase in insulin secretion. The major side effects are hypoglycaemia and weight gain. They are preferred in those patients who are of normal weight or only moderately obese (BMI <27Kg/m2), or those intolerant of metformin. Choices include Tolbutamide 500mg-1g tds or Gliclazide 80-160mg bd. Glibenclamide 2.5-15mg daily should not be used in those aged over 65 years because its prolonged action increases the risk of hypoglycaemia.
Meglitinides – Repaglinide (0.5-4mg tds) and Nateglinide (120mg tds) are short-acting glucose-lowering drugs that acts similarly to the sulphonylureas and have similar efficacy. Repaglinide is licensed for use alone whereas Nateglinide is licensed for use with Metformin only. They are considerably more expensive than the sulphonylureas, and the only real therapeutic advantage is less weight gain. Hypoglycaemia is a potential risk.
Alpha-glucosidase inhibitor – Acarbose (50-100mg tds) modifies intestinal absorption of carbohydrate but is rarely tolerated because of GI side effects.
Thiazolidinediones (Glitazones)
– Please also refer to NICE Technology Appraisals 9 and 21
The thiazolidinediones, rosiglitazone (4mg daily) and pioglitazone (30mg daily), lower blood glucose concentrations by increasing insulin sensitivity (PPAR-? agonists). The first drug in this class, troglitazone was removed from the market in the United Kingdom because of reports of hepatic injury that was either fatal or necessitated liver transplantation. Rosiglitazone and pioglitazone have less hepatotoxicity, although experience with these drugs is still limited and the NICE review recommends checking liver function tests every 2 months in the first year of treatment. They are for combination therapy with metformin or a sulphonylurea. Thiazolidinediones are no more effective than metformin (or in combination with a sulphonylurea). They are also associated with more weight gain than metformin, and are considerably more expensive than any of the other oral hypoglycaemic drugs. As a result, their main use is probably in patients who have contraindications to metformin (due to gastrointestinal side effects or a high serum creatinine concentration). Pioglitazone may have an advantage in patients with hyperlipidaemia.
Obesity Drugs- Orlistat (Xenical) (please also refer to NICE Technology Appraisal 22) is a minimally absorbed drug that inhibits the activity of pancreatic and gastric lipases, blocking absorption of approximately 30 percent of ingested fat. It is associated with significant weight loss, accompanied by improvement in blood glucose control in diabetic subjects. However, the weight loss seems to be most prominent in the first 6 to 12 months, after which weight regain can occur. Sibutramine (Reductil) (please also refer to NICE Technology Appraisal 31) is an active monoamine re-uptake inhibitor recently licensed for the treatment of obesity for up to one year. When taken in combination with dietary advice and support, it produces 5-7% weight loss. The side effects include tachycardia and hypertension.