Place of SGLT2 Inhibitors in Treatment Paradigms for T2D
Since its introduction in early 2013, this class of drugs has been the subject of excitement in the T2DM therapeutic area, and we have gained significant clinical experience in a relatively short time. This is most likely attributable to the prompt efficacy of the class; although it was perhaps not immediately apparent from the clinical trial evidence, the effect of SGLT2 inhibitors on serum glucose levels appears to occur more quickly than with most available anti-hyperglycemia drugs. Based on their mode of action, SGLT2 inhibitors reduce glucose levels practically as soon as the agent appears in the serum, and no other glucose-lowering drug except intravenous insulin has the capability to work so fast. Because there is a prompt lowering of glucose levels, the demand for insulin is immediately reduced, resulting in less variability, improved response, and less hypoglycemia.
The SGLT2 inhibitor class has been quickly adopted by endocrinologists and diabetes experts. It has been incorporated into the AACE/ACE 2015 comprehensive diabetes management algorithm, as well as the AACE/ACE clinical guidelines and the recently updated ADA/EASD guidelines. In accordance with FDA-approved indications, SGLT2 inhibitors have been used by many as initial monotherapy and in combination with metformin, sulfonylureas, and DPP-4 inhibitors. Although not extensively studied, many physicians have used SGLT2 inhibitors in combination with metformin and GLP-1 receptor agonists, allowing not just for glucose control but also for potentially significant weight loss without hypoglycemia. Although not indicated to control hypertension, this type combination may also significantly reduce blood pressure.
This author's clinical experience also suggests that SGLT2 inhibitors may be a useful therapy for patients with late-onset autoimmune diabetes of adulthood (LADA). Such patients are initially diagnosed with T2DM in later life but swiftly become insulin dependent. Diagnosis of LADA is generally confirmed by an assay for glutamic acid decarboxylase antibodies. In patients with LADA, an SGLT2 inhibitor given in addition to basal insulin may reduce A1C and moderate daily glucose variability and spikes. Clinical trials of SGLT2 inhibitors have not excluded patients with LADA, and such individuals are likely to have participated in the evaluations. Nonetheless, these patients may be similar to people with T1DM and the clinician may elect to wait for the results of prospective trials in this population that would further test this hypothesis and establish safety.
Clinical Observations
Since its introduction in early 2013, this class of drugs has been the subject of excitement in the T2DM therapeutic area, and we have gained significant clinical experience in a relatively short time. This is most likely attributable to the prompt efficacy of the class; although it was perhaps not immediately apparent from the clinical trial evidence, the effect of SGLT2 inhibitors on serum glucose levels appears to occur more quickly than with most available anti-hyperglycemia drugs. Based on their mode of action, SGLT2 inhibitors reduce glucose levels practically as soon as the agent appears in the serum, and no other glucose-lowering drug except intravenous insulin has the capability to work so fast. Because there is a prompt lowering of glucose levels, the demand for insulin is immediately reduced, resulting in less variability, improved response, and less hypoglycemia.
The SGLT2 inhibitor class has been quickly adopted by endocrinologists and diabetes experts. It has been incorporated into the AACE/ACE 2015 comprehensive diabetes management algorithm, as well as the AACE/ACE clinical guidelines and the recently updated ADA/EASD guidelines. In accordance with FDA-approved indications, SGLT2 inhibitors have been used by many as initial monotherapy and in combination with metformin, sulfonylureas, and DPP-4 inhibitors. Although not extensively studied, many physicians have used SGLT2 inhibitors in combination with metformin and GLP-1 receptor agonists, allowing not just for glucose control but also for potentially significant weight loss without hypoglycemia. Although not indicated to control hypertension, this type combination may also significantly reduce blood pressure.
This author's clinical experience also suggests that SGLT2 inhibitors may be a useful therapy for patients with late-onset autoimmune diabetes of adulthood (LADA). Such patients are initially diagnosed with T2DM in later life but swiftly become insulin dependent. Diagnosis of LADA is generally confirmed by an assay for glutamic acid decarboxylase antibodies. In patients with LADA, an SGLT2 inhibitor given in addition to basal insulin may reduce A1C and moderate daily glucose variability and spikes. Clinical trials of SGLT2 inhibitors have not excluded patients with LADA, and such individuals are likely to have participated in the evaluations. Nonetheless, these patients may be similar to people with T1DM and the clinician may elect to wait for the results of prospective trials in this population that would further test this hypothesis and establish safety.
Source...