Diabetes Mellitus Treatments

Diabetes Mellitus Treatments

Insulin

Insulin has the highest efficacy – this makes sense, since insulin deficiency is the root of the pathology in diabetes mellitus.
Insulin allows glucose uptake and utilization in key tissues.
Rapid, regular (or "short"), intermediate, and long-acting versions of insulin that are given in different patient scenarios.
Insulin does have potential hypoglycemic effects; the risk is higher when human insulin is used.
Cardiovascular effects are neutral.
Give lower doses of insulin when a patient's estimated GFR is low.
Insulin is often administered into subcutaneous tissues via injections or continuously via an insulin pump; an inhaled version with rapid action can be used before meals.
Cost varies by type of insulin and route of administration; for simplicity, indicate that human insulin costs less than analog insulin.

In the US, especially, the price of insulin is an impediment to proper diabetes management.

Patients with Type 1 diabetes: insulin is a required treatment and must be taken regularly throughout the day, with special considerations given to infection and surgery.
Patients with Type 2 diabetes: may not need insulin if their glucose levels are controlled by other medications and/or changes in diet and exercise. However, when glucose targets are not met by these measures, patients will need insulin.
Weight gain is a common side effect of insulin use.

Metformin

A highly effective drug that reduces hepatic gluconeogenesis as a means of reducing blood glucose levels.
It does not cause hypoglycemia.
Metformin seems to have beneficial effects on cardiovascular outcomes, though more conclusive studies are needed.
Metformin doesn't seem to affect the development of chronic kidney disease, but is contraindicated in patients with low estimated GFR (eGFR < 30 mL/min/1.73m2).
This drug is administrated orally, and is relatively low in cost.
Metformin is first-line therapy in patients with Type 2 diabetes.
Side effects include gastrointestinal issues (nausea, vomiting), and there is potential for vitamin B12 deficiency.

Second generation sulfonylureas

Highly effective drugs that increase insulin secretion via beta cell stimulation. They do this by interacting with the sulfonylurea receptors, which reduce cellular potassium release; this depolarizes the cell and triggers insulin release.
Because sulfonylureas increase insulin release, they can cause hypoglycemia.
They have neutral effects on ASCVD, heart failure, and diabetic kidney disease.
Administration is orall, and cost is relatively low.
These drugs can cause weight gain (like insulin does), and, despite being the second most prescribed drug for diabetes treatment, these drugs are associated with increased risk of cardiovascular event and mortality.

SGLT-2 inhibitors

Intermediate efficacy.
These drugs decrease blood glucose levels by increasing glucose output in the urine. They do this by inhibiting the sodium-glucose co-transports and blocking glucose reabsorption in the nephron.
They do not produce hypoglycemia.
Empagliflozin, canagliflozin and dapagliflozin have beneficial effects on ASCVD, Heart Failure, and diabetic kidney disease.

Cardioprotective effects include reducing blood pressure, producing osmotic diuresis, and improving cardiac energy metabolism, among others. It is also thought that SGLT-2 inhibitors protect the kidneys via reductions in renal blood flow, glomerular hyperfiltration, and intra-glomerular pressure.

Oral administration
Unfortunately, their high cost is prohibitive for many.
SGLT-2 inhibitors should be discontinued prior to surgery to avoid diabetic ketoacidosis.
They are associated with weight loss, bone fractures, urogenital infections, volume depletion and hypotension, increases in LDL levels, and increased risk of Fournier's gangrene and necrosis of the lower limb leading to foot and leg amputation.

GLP-1 receptor agonists

Highly effective drugs that increase insulin secretion by stimulating receptors for Glucagon-Like-Peptide-1, which is an incretin that facilitates pancreatic release of insulin.

Does not have hypoglycemic effects.
Dulaglutide, liraglutide, and semaglutide have protective effects against ASCVD and diabetic kidney disease.
Administration can be subcutaneous injection or orally.
These drugs are also expensive.
They are associated with weight loss and gastrointestinal side effects.
Risk of acute pancreatitis has long been suspected, but recent studies cast doubt on the relationship between GLP1-receptor agonists and pancreatitis.

DPP-4 inhibitors (dipeptidyl-peptidase 4 inhibitors)

Intermediate efficacy.
These drugs increase incretin levels which, as stated above, increase insulin secretion.

These drugs do not have hypoglycemic effects.
Initial studies indicated an increased risk of heart failure with the DPP-4 inhibitor saxagliptin, but follow-up studies were unable to replicate this finding with this or other versions of the drug.
Renal disease effects are neutral.
Indicate that administration is orally, and cost is high.
Some studies have found an association between DPP-4 inhibitor use and pancreatitis, but causal links are elusive.

Thiazolidinediones

Highly effective drugs that improve insulin sensitivity, increase fatty acid uptake, and promote adipogenesis.
They do not have hypoglycemic effects.
They are associated with increased risk of heart failure, and can cause fluid retention; thus, do not give to patients with renal impairment.
Administration is orally and cost is relatively low.
In addition to the increased risk of heart failure, these drugs are also associated with weight gain, bone fractures, bladder cancer, increased LDL, and, as mentioned fluid retention.