Went to the practice clinical meeting, which was about diabetes this time and mainly focused on new diabetes drugs, as well as going over the NICE guidelines. The meds covered were incretin-based therapies (GLT-1 agonists and DPP-4 inhibitors) which I have previously made notes on, and SLGT-2 inhibitors which I’ve had next to nothing to do with. The meeting was sponsored by Novo Nordisk.
Points about SLGT-2 inhibitors, and some new points aobut DPP-4 inhibitors:
Dapagliflozin, canagliflozin and empagliflozin (others in the pipeline). Inhibit sodium-glucose co-transporters, which absorb glucose from the small intestine and reabsorb it from the glomerular filtrate. They also manage the uptake and release of glucose from all cells in the body, including uptake across the blood-brain barrier. As the number suggests, there are two different types; SLGT-2 are the ones primarily responsible for renal absorption (mutations in the gene are the cause of familial renal glycosuria, which is typically asymptomatic, hence the inspiration for the SGLT-2 inhibitor).
SLGT-2 inhibitors will also slightly reduce weight and systolic BP. Canagliflozin seems to be slightly more effective in terms of both body weight reduction and HbA1c reduction, but that seems to be based on individual pharmaceutical company studies and not on head-t0-heads, and it also has more interactions; all of them interact with diuretics, insulin, and insulin secretagogues, but canagliflozin also interacts with enzyme inducers, cardiac glycosides, dabigatran, and simvastatin and rosuvastatin.
There do not seem to be any data on outcome measures.
Their renal-focused mode of action means that they are low risk for hypoglycaemia, but sensitive to the effects of renal impairment. They should only be started if eGFR is 60 or higher, although, in a patient whose eGFR deteriorates while already taking an SLGT-2 inhibitor, canagliflozin and empagliflozin can be continued down to an eGFR of 45 ml/min/1.73 m^2. They are also associated with increased risk of side-effects in the elderly and have age limits on them.
There is a risk of them leading to ketoacidosis when used in Type 2 DM and patients should be aware of the symptoms; DIB, nausea/vomiting, abdo pain, confusion, unusual fatigue/sleepiness.
These, I already wrote about here. Other points, applicable as of Nov 2016:
- All except Alogliptin can be used as monotherapy.
- All can be used as dual therapy with metformin, sulfonylurea, TZD, or insulin.
- All can be used as triple therapy with insulin and metformin.
- All except Alogliptin can be used as triple therapy with metformin and sulfonylurea.
- Sitagliptin and Alogliptin can be used as triple therapy with metformin and TZD.
- Linagliptin doesn’t seem to have any side-effects listed. I don’t know how new it is, however.
- The others, except for saxagliptin, have hypoglycaemia listed under common side-effects. Saxagliptin lists myalgia and gastritis. Sitagliptin is the only one to list constipation, which became relevant shortly after the meeting when I had to prescribe a DPP-4 inhibitor for a patient who already had constipation problems and didnt’ want to take anything that was likely to make it worse. All of them can cause headaches and nausea.
- They carry a risk of acute pancreatitis.