Type 2 diabetes: The management of type 2 diabetes

4.1 Glucose control: oral glucose-lowering therapy

Metformin: confirmatory studies of the advantage in terms of cardiovascular outcome studies.

Why this is important

The UKPDS study confirmed that metformin offered cardiovascular protection. However, the extent of the relative risk reduction was unexpectedly large and needs formal testing in a further study. This is critical to the positioning of metformin in the treatment cascade.

4.2 Glucose control: oral glucose-lowering therapy

Studies of the role of sulfonylureas when starting a pre-mixed insulin preparation.

Why this is important

Both pre-mixed insulins and sulfonylureas are effective glucose-lowering agents throughout the day, but can cause hypoglycaemia. When starting insulin, continuing sulfonylureas prevents deterioration of glucose control during insulin dose titration and reduces the requirement for insulin. However, it is not clear that these advantages are not offset by an increased risk of hypoglycaemia.

4.3 Self-monitoring of plasma glucose

Longer-term studies of the role of self-monitoring as part of an integrated package with patient education and therapies used to target.

Why this is important

Studies of self-monitoring, in people not using insulin, continue to fail to address the complicated issue of its integration into patient education and self-management behaviours. Self-monitoring can be moderately expensive and a significant burden if not used appropriately. While it is accepted that study designs are difficult in this area, the positive results from large observational studies need further support.

4.4 Blood-pressure-lowering medications

The use of ACE inhibitors and angiotensin II-receptor antagonists in combination in early diabetic nephropathy.

Why this is important

Both of these classes of renin–angiotensin system blockers are effective in reducing the rate of progression of diabetic kidney damage. However, there are acute risks of side effects associated with both classes of drug. As these risks are similar, it is not clear whether the expected combined benefit from ACE inhibitors and angiotensin II-receptor antagonists would outweigh the combined risks.

4.5 Diabetic neuropathic pain management

Comparison studies on tricyclic drugs, duloxetine, gabapentin and pregabalin.

Why this is important

While all these drugs are partially effective in the control of neuropathic pain, they differ in cost and side-effect profile. This makes the recommendations of treatment cascade uncertain to some extent. There is a need for comparative studies between these drugs and, in particular, of the newer agents with the tricyclic drugs.

The Guideline Development Group that developed the recommendations in sections 1.6 and 1.7.2 on newer agents for blood glucose control made the following recommendations for research.

4.6 Effectiveness and safety of GLP-1 mimetics

Studies of the effectiveness and safety of GLP-1 mimetics (with and without insulin) in the long-term management of blood glucose.

Why this is important

There is a lack of long-term evidence (12 months or longer) on the clinical and cost effectiveness of GLP-1 mimetics compared with standard UK practice or other newer agents. There is also limited evidence on the effect of replacing insulin with a GLP-1 mimetic and it is not clear whether some subgroups would benefit from this more than others. GLP-1 mimetics do not currently have UK marketing authorisation for use with insulin, but there is anecdotal evidence that this combination is being used. More evidence is needed on safety and effectiveness.

4.7 Effectiveness of DPP-4 inhibitors

Studies of the clinical and cost effectiveness of DPP-4 inhibitors in the long-term management of blood glucose.

Why this is important

There is a lack of long-term evidence (12 months or longer) on the clinical and cost effectiveness of DPP-4 inhibitors compared with standard UK practice or other newer agents. It is not clear whether there are any subgroups in which DPP-4 inhibitors are more clinically and cost effective.

4.8 Adherence with different complexities of treatment regimen

Studies of how adherence varies with complexity of treatment regimen.

Why this is important

Adherence to treatment is important for clinical (blood glucose control) and patient (health-related quality of life) outcomes. There are currently few data on how the complexity of treatment regimen affects adherence.

4.9 Health-related quality of life

Studies to investigate how the initiation and titration of long-acting insulin affects health-related quality of life, the changes associated with hypoglycaemia and the direct affect of weight loss or avoiding weight gain.

Why this is important

Heath-related quality of life is an important determinant of adherence to treatment.