Clinical Trials in Older Patients with Frailty Syndrome a Need for Evidence Based Studies

Markolf Hanefeld, Centre for Metabolic Vascular Medicine, GWT-Technical University Dresden
Dresden, Germany

Frailty is a common state of increased vulnerability and impaired capacity of homeostasis in multimorbid older patients with diabetes. About 60-80 % of patients with type 2 diabetes suffer from metabolic syndrome associated with a high prevalence of chronic kidney disease, cardiovascular disease, heart failure, cognitive deficits / dementia and sarcopenia. Sarcopenia leads to degenerative loss of muscle mass, muscle strength, osteopenia and immobility. In a vicious cycle this leads to a progressive deterioration of mental and physical fitness and at least to loss of autonomy and excessive mortality.

In countries with western life style more than 10 % of people older than 70 years suffer from type 2 diabetes with a high risk of frailty.

So far studies of diabetes control and cardiovascular outcome trials (CVOTs) focus on major cardiovascular events and mortality with a majority of patients < 70 years. Clinical trials with antidiabetic drugs take HbA1c control, risk of hypoglycemia and weight loss as criteria for benefit.

Targets and expectations of older patients however are different from individuals included in CVOTs. Moreover HbA1c control < 8 % has little or no effect on cardiovascular complications and life expectancy. For these older patients with multimorbidity there are other priorities:

  1. Improved quality of life
  2. Physical and mental fitness
  3. Protection from renal failure and foot syndrome
  4. Safety
  5. Practicability

Thus, studies with antidiabetic drugs must be planned on the basis of best life style intervention and control of major risk factors in elderly patients including blood pressure control, statin treatment etc.

Multimorbidity always requires polypharmacy. Thus, we need composite endpoints. Two types of studies are urgently needed:

(1)   Hard endpoints of end-organ benefit and mortality if life expectancy
> 5 years (primary prevention of frailty)

(2)   Secondary prevention of frailty progress as primary objectives

In conclusion frailty is a multidimensional geriatric syndrome that needs an integrated approach. However, benefit risk of intervention measures must be evaluated to avoid a polypharmacy with adverse effects and high costs.