DiaFrail: A Short Duration Study in Older People ( DIAFRAIL Study) — DiaFrail  

Diabetes Mellitus Clinical Trial

Official title: A 16 Week PILOT Study to Determine the Frequency of Sulphonylurea-Associated Hypoglycaemia in Older Moderately Frail Patients With Type 2 Diabetes Mellitus Poorly Controlled on Metformin: an Open Label Study ( DIAFRAIL Study)

Status Withdrawn

Clinical Trial Summary

1. Many patients with type 2 diabetes are not at glycaemic goal and require additional therapy in order to reduce vascular risk and improve symptom control

2. Sulphonylurea therapy is a commonly prescribed 2nd-line glucose -lowering agent and its use is recommended in major clinical guidelines for diabetes and also in the recently presented IDF (International Diabetes Federation) guidelines for older people.

3. Older people with diabetes are not a homogeneous group and as many as 25% are frail.

4. Frailty is a PRE-DISABILITY state but may increase the 'vulnerability' of many older people to having a fall, admission into hospital, or perhaps increasing their risk of hypoglycaemia

5. As a consequence of their glucose-lowering ability, sulphonylureas may increase the risk of hypoglycaemia in older people and those who have features of frailty may be at increased risk.

6. The investigators therefore need to estimate the risk of hypoglycaemia in moderately frail older subjects with type 2 diabetes who are taking sulphonylurea therapy as this is a commonly prescribed class of agent used routinely in clinical practice

7. Thus, this short term project wishes to assess the frequency of hypoglycaemia in subjects with some evidence of frailty with type 2 diabetes by a series of glucose monitoring techniques with excellent research team support to minimize any safety issues. An identical study at the Second University of Naples, Italy under the supervision of Professor Giuseppe Paolisso is planned and is the second study site for this PILOT project.

Clinical Trial Description

Rationale for Study

The rates of hypoglycaemia in older people with diabetes are not known with any accuracy and there are no data in older frail patients with diabetes. However, as this latter group is increasingly recognized as a specific subgroup of patients with diabetes it is important to assess how safe sulphonylurea agents are in older patients as this group of glucose-lowering medication is recommended in most diabetes clinical guidelines including algorithms.

The data for rates of mild to moderate hypoglycemia in older people with diabetes is also very scant and because many episodes may be asymptomatic, these take place without either the patient or family knowing, and thus important information of this nature does not reach the clinician in charge of prescribing. In these latter circumstances, continuous blood glucose monitoring (CBGM) will have an important role to detect the frequency of these episodes and will be used in a subgroup of each treatment arm in this PILOT study. When hypoglycaemic episodes are accompanied with symptoms, detection rates are obviously improved. It is important note that even mild symptomatic hypoglycemia may be associated with increased cardiovascular events, increased hospitalisation and increased mortality although this study was in a young 'elderly' group (average age about 63y), There is thus an important need to assess what this risk is and whether commonly used sulphonylureas are relatively safe in this respect. As metformin and sulphonylureas are still the commonest agents used to lower glucose levels in people with diabetes, the investigators wish to study these first in our programme of studies in this area. With the development of other classes of oral glucose-lowering agents such as DPP4-inhibitors which are associated with low levels of hypoglycaemia and are well tolerated in older patients with type 2 diabetes (5), it is important to provide more justification for their use by discovering if hypoglycaemia, both subclinical/asymptomatic and more serious forms of hypoglycaemia occur commonly in sulphonylurea treatment.

The data for rates of mild to moderate hypoglycemia in older people with diabetes is even more scant - when symptomatic, detection rates are improved, but when asymptomatic, detection requires CBGM. In a young 'elderly' group (average age about 63y), even mild symptomatic hypoglycemia may be associated with increased cardiovascular events, increased hospitalisation and increased mortality Therefore, the primary object of this short PILOT hypoglycemia rate-determining study will be the evaluation of the difference (as % of variation of mild-moderate hypoglycemic events) between glimepiride (2-4mg twice daily) as add on to metformin, and metformin treatment alone (at maximal dose (1500 mg/day), in mild to moderately frail older type 2 diabetic patients aged over 70 years. The investigators will wish to observe whether the intervention group has had a change in HbA1c levels during the treatment period with glimepiride. ;

Related Conditions & MeSH terms

• Diabetes Mellitus

• NCT number: NCT02484209
• Study type: Interventional
• Source: Diabetes Frail Ltd
• Status: Withdrawn
• Phase: Phase 3
• Start date: February 2016
• Completion date: November 2016