The Use of Liraglutide in Obese People With Type 1 Diabetes
The Use of Liraglutide in Obese People With Type 1 Diabetes
Under this tightly observed protocol, in motivated patients with type 1 diabetes, under close clinical supervision (and by whatever mechanisms of action), significant weight reduction occurred without metabolic destabilisation. Clinically and statistically significant reductions in insulin dosages were achieved which appeared to be a consequence of the weight loss, possibly indicative of an improvement in insulin resistance as determined by the crude measure of the changes in units/kg. Perhaps disappointingly, attainment of glycaemia, did not improve. This at least allowed the true potential for weight loss to emerge independent of changes that might have resulted from sharp improvements or deteriorations in glycaemic control. The magnitude of weight loss in this group appeared to exceed that expected in type 2 diabetes, possibly because of the interplay of GLP-1 effects together with the reduced pro-obesity effect of falling insulin dosage. It is possible that weight loss might not have been so good if we had simultaneously achieved a significant HbA1c reduction, and it is known that intensification of insulin therapy to attain good control is associated with weight gain. Interestingly, we observed a similar amplification effect when adding GLP-1 agonist therapy to those already on insulin therapy in type 2 diabetes.
The individual variation of responses was of clinical importance. One patient had poor tolerability. Otherwise it can be seen that an effective response was clearly evident very early in the use of GLP-1 agonist therapy and, equally, non-responsiveness in a single patient was similarly obvious by 3 months.
Ethical issues around unlicensed uses of liraglutide in type 1 diabetes must focus on safety. Our preliminary experience is reassuring, but it is small scale and provides no more than a cautious "proof of concept" amongst the few other small-scale trials that have been published. There are no currently available data to suggest harm over and above the standard cautions and side effects understood and observed in mainstream clinical practice. Large, prospectively randomised studies have started to explore the role of liraglutide as additional treatment in type 1 diabetes. Until they report, we would urge colleagues not to embark on this therapy without due regard to all local clinical governance processes, tight systems of clinical supervision, clear mechanism for independent peer review and a fully informed and consented patients, who have appropriate (and assessed and documented) levels of self-care proficiency.
We conclude that, under the appropriate conditions, and with appropriate patient selection, GLP-1 agonist therapy in type 1 diabetes may be advantageous where weight reduction becomes both a constraint and a therapeutic objective.
Discussion
Under this tightly observed protocol, in motivated patients with type 1 diabetes, under close clinical supervision (and by whatever mechanisms of action), significant weight reduction occurred without metabolic destabilisation. Clinically and statistically significant reductions in insulin dosages were achieved which appeared to be a consequence of the weight loss, possibly indicative of an improvement in insulin resistance as determined by the crude measure of the changes in units/kg. Perhaps disappointingly, attainment of glycaemia, did not improve. This at least allowed the true potential for weight loss to emerge independent of changes that might have resulted from sharp improvements or deteriorations in glycaemic control. The magnitude of weight loss in this group appeared to exceed that expected in type 2 diabetes, possibly because of the interplay of GLP-1 effects together with the reduced pro-obesity effect of falling insulin dosage. It is possible that weight loss might not have been so good if we had simultaneously achieved a significant HbA1c reduction, and it is known that intensification of insulin therapy to attain good control is associated with weight gain. Interestingly, we observed a similar amplification effect when adding GLP-1 agonist therapy to those already on insulin therapy in type 2 diabetes.
The individual variation of responses was of clinical importance. One patient had poor tolerability. Otherwise it can be seen that an effective response was clearly evident very early in the use of GLP-1 agonist therapy and, equally, non-responsiveness in a single patient was similarly obvious by 3 months.
Ethical issues around unlicensed uses of liraglutide in type 1 diabetes must focus on safety. Our preliminary experience is reassuring, but it is small scale and provides no more than a cautious "proof of concept" amongst the few other small-scale trials that have been published. There are no currently available data to suggest harm over and above the standard cautions and side effects understood and observed in mainstream clinical practice. Large, prospectively randomised studies have started to explore the role of liraglutide as additional treatment in type 1 diabetes. Until they report, we would urge colleagues not to embark on this therapy without due regard to all local clinical governance processes, tight systems of clinical supervision, clear mechanism for independent peer review and a fully informed and consented patients, who have appropriate (and assessed and documented) levels of self-care proficiency.
We conclude that, under the appropriate conditions, and with appropriate patient selection, GLP-1 agonist therapy in type 1 diabetes may be advantageous where weight reduction becomes both a constraint and a therapeutic objective.