The team also looked at subgroup analyses comparing SUs versus dipeptidyl peptidase (DPP)-4 inhibitors (n=9114) and versus thiazolidinediones (TZD; n=1873).

This “is particularly notable as sulfonylureas and thiazolidinediones are generally associated with weight gain,” remark Chin et al.

People aged 60 years or older receiving thiazolidinedione monotherapy for type 2 diabetes may have a lower risk for dementia than those taking metformin monotherapy, an observational study suggests.

Related news story: SUSTAIN 1: ‘high degree’ of glycemic control with semaglutide in type 2 diabetes SUSTAIN 2: Published Trial population: type 2 diabetes, taking metformin and/or thiazolidinediones Comparator treatment: sitagliptin https://clinicaltrials.gov/ct2/show/NCT01930188 SUSTAIN 2, also published in The Lancet Diabetes & Endocrinology , in April 2017, was a head-to-head study of weekly injectable semaglutide versus daily oral sitagliptin in patients already taking metformin and/or thiazolidinediones.

The exceptions were dipeptidyl peptidase-4 inhibitors for mortality and thiazolidinediones for all outcomes, although there were nonsignificant trends toward a reduced risk.

Researchers have used data from clinical practice and randomized trials to identify simple predictors of patient response to sulfonylureas and thiazolidinediones.

This revealed that glucagon-like peptide (GLP)-1 receptor agonists and thiazolidinediones significantly reduced stroke risk, by 15% and 18%, respectively, but other medication classes had no significant effect.

The SUSTAIN 2 findings show that the glucagon-like peptide-1 analog semaglutide produces better glycemic control than the dipeptidyl peptidase-4 inhibitor sitagliptin in patients achieving inadequate control with metformin, thiazolidinediones, or both.

In my tool box I had three sulfonylureas, two thiazolidinediones, a couple of formulations of metformin, and human insulin.

The most commonly chosen OADs were sodium-glucose cotransporter (SGLT)2 inhibitors (47.9%), followed by dipeptidyl peptidase (DPP)-4 inhibitors (39.7%), sulfonylureas (10.8%), thiazolidinediones (1.1%), and α-glucosidase inhibitors (0.5%).

In ADOPT, among the 3967 participants recently diagnosed with type 2 diabetes, 1343 were taking metformin, 1289 sulfonylureas, and 1335 thiazolidinediones.

In line with these trends, the use of diabetes medications rose by 8.6 percentage points until the 2007–2010 period, but then leveled off, although this obscured some shifts such as a rise in use of the newer medication classes and declining use of sulfonylureas and thiazolidinediones.

Medication Benefits of use Risks of use Metformin Low risk hypoglycaemia, well tolerated Risk in renal impairment (dehydration), gastrointestinal side effects, comorbidities can limit use Sulfonylureas Quick glucose stabilisation, relatively well tolerated Increased risk of hypoglycaemia, especially if comorbidities, risk of heart failure Thiazolidinediones Useful but limited glycaemic control Long-term effects (cardiovascular/bladder/fracture risk) Meglitinides Rapid insulin promoting action, useful in erratic eaters, possible lower risk hypoglycaemia Limited availability, cost DPP-4 inhibitors Benefit especially in renal impairment, low risk hypoglycaemia Moderate glycaemic improvement GLP-1 agonists Low risk hypoglycaemia, good glycaemic improvement Weight loss may not be ideal, satiety effects not ideal, gastrointestinal side effects, cost benefit, may not be effective at late stage SGLT-2 inhibitors Good glycaemic improvement but avoid Risk of dehydration, UTIs/thrush and confusion, comorbidities limit use UTI=urinary tract infection.

Bonora stressed that TOSCA.IT (Thiazolidinediones Or Sulfonylureas Cardiovascular Accidents Intervention Trial) is the only published trial offering a head-to-head comparison of these currently available drugs, with only one other (CAROLINA) on the horizon.

Antiglycemic therapies among those being treated included: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide-1 receptor agonists (4%); SGLT2 inhibitors (2%); and thiazolidinediones (2%).

Risk of hypoglycemia Low Moderate High Metformin Metglinides Insulin Thiazolidinediones Sulfonylureas DPP-4 inhibitors GLP-1RA Alpha-glucosidase inhibitors Colesevelam Bromocriptine SGLT2-inhibitors DPP-4, dipeptidyl peptidase-4; GLP-1RA, glucagon-like peptide-1 receptor agonists; SGLT2, sodium-glucose cotransporter-2.

An umbrella review of meta-analyses has demonstrated mixed associations between different glucose-lowering agents and cardiovascular outcomes in people with type 2 diabetes, with the results favoring sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists as cardioprotective agents.

Sulfonylureas, thiazolidinediones, and insulin were grouped as promoting weight gain.

Looking at the 1-year response to treatments, which in ADOPT were sulfonylureas, thiazolidinediones, and metformin, the researchers found variation between the four subgroups for the first two, but not the last.