After seven years, the American College of Physicians recently released a new version of the "Guidelines for the Drug Treatment of Type 2 Diabetes in Adults", which gives new clinical recommendations for the use of diabetes in the guidelines based on the clinical evidence of diabetes medication accumulated in recent years.
The new guidelines are an update of the 2017 version of the guidelines, mainly based on the clinical data in recent years, the clinical evidence on the effectiveness and harm of new treatment drugs for diabetes, with the goal of reducing all-cause mortality, cardiovascular disease incidence, and the risk of chronic kidney disease progression in patients with type 2 diabetes.
Newer drugs in recent years include glucagon-like peptide-1 (GLP-1) agonists (semaglutide, dulaglutide, exenatide, and semaglutide, among others), GLP-1 agonists, and glucose-dependent insulinotropic polypeptide agonists (tirzepatide), sodium-glucose cotransporter-2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin, and erpagliflozin), dipeptidyl peptidase-4 (DPP-4) inhibitors (alogliptin, linagliptin, saxagliptin and sitagliptin) and long-acting insulin (insulin), insulin glargine and insulin degludec. Based on the effectiveness of these drugs and the clinical evidence for reducing the risk of diabetes complications, new guideline recommendations have been made for these drugs.
In this guideline, there are 3 recommendations with high-quality evidence and high recommendation level that deserve our attention -
- Metformin (unless contraindicated) and lifestyle changes are the first steps in managing type 2 diabetes in most patients.
- A sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist is recommended in adults with metformin and inadequate glycemic control.
- Addition of dipeptidyl peptidase-4 (DPP-4) inhibitors to adults with metformin and inadequate glycemic control and lifestyle changes are not recommended to reduce morbidity and all-cause mortality.
Metformin remains the initial treatment of choice
Metformin is still used as a first-line drug for the management of diabetic patients with the same importance as lifestyle changes, and this recommendation is based on many considerations, first of all, if patients with type 2 diabetes are still unable to control their blood sugar under the premise of doing a good job in life conditioning, metformin is the first choice as the initial drug, whether it is from the safety and tolerability of the drug, or from the hypoglycemic effect, medication and refinement, etc., it is currently worth recommending. Compared with other new drugs, metformin is one of the ideal drugs for blood sugar control in patients with type 2 diabetes due to its high accessibility, low price, low drug cost, clear hypoglycemic effect, and high drug safety.
For most people with type 2 diabetes, the goal is to reduce glycosylated hemoglobin levels by 7% to 8%, and for some glycosylated hemoglobin levels to less than 6.5% For some diabetic patients with low blood sugar elevation, metformin alone can achieve the above hypoglycemic goals, and the risk of hypoglycemia is low, and it will not cause the patient's drug burden, therefore, the initial treatment of patients with type 2 diabetes, in the absence of contraindications, it is still recommended to take metformin.
Glycemic control is poor, and a combination of SGLT2 inhibitors or GLP-1 agonists is recommended
For patients who are well adjusted in their lifestyle and take metformin alone and still have poor blood glucose control, the guidelines recommend that SGLT2 inhibitors or GLP-1 receptor agonist hypoglycemic drugs are used in combination to enhance the hypoglycemic effect and protect the heart and kidney.
SGLT2 inhibitor drugs are what we often call dapagliflozin, empagliflozin, canagliflozin and other drugs, while GLP-1 agonist drugs include the well-known semaglutide, dulaglutide, exenatide and other drugs.
After summarizing a number of clinical data, the guidelines state that-
•The use of SGLT-2 inhibitors reduces the risk of all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization for congestive heart failure.
•The use of GLP-1 agonists reduces the risk of all-cause mortality, major adverse cardiovascular events, and stroke. (See image below)
Green indicates the presence of clinical benefit
That is to say, for patients with type 2 diabetes, the combination of the above two drugs on the basis of metformin not only strengthens the hypoglycemic effect, but also brings more benefits in the prevention of diabetes complications. Clinical evidence suggests that SGLT-2 inhibitors and GLP-1 agonists reduce all-cause mortality compared with newer long-acting insulins, and that SGLT-2 inhibitors reduce the risk of major cardiovascular events compared with DDP-4 inhibitors, SGLT-2 inhibitors reduce the risk of major cardiovascular events compared with sulfonylureas (gliclazide, glimepiride, etc.), and have a lower risk of severe hypoglycemia compared with sulfonylureas and insulin。
When economic considerations were added, the committee noted that there was no significant difference between SGLT-2 inhibitors and GLP-1 agonists, and therefore the pharmacological implications of clinical benefit should be prioritized in the choice of these two agents. However, for our Chinese patients, some SGLT-2 inhibitor drugs have been included in the centralized procurement catalog, and all GLP-1 receptor agonist drugs are relatively expensive, and the former may be more advantageous in terms of cost-benefit ratio.
DPP4 inhibitors are not recommended?
Another major update in the guidelines is that for DPP4 inhibitors such as alogliptin, sitagliptin, and linagliptin, the guidelines do not recommend it as a combination drug option for metformin, and it is also a choice based on clinical evidence.
High-quality evidence suggests that there is no difference between the combination of DPP4 inhibitors in all-cause mortality, major cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, and progression of chronic kidney disease compared with conventional metformin treatment, while DPP4 inhibitors increase the risk of hospitalization for heart failure and the risk of progression of chronic kidney disease compared with the two classes of drugs recommended above.
In fact, this kind of drug is not recommended by the guidelines for the treatment of patients with heart failure, mainly based on the evidence of clinical benefits, especially compared with SLGT2 inhibitors and GLP-1 agonists, it lacks clinical benefits, but as a hypoglycemic drug with good hypoglycemic effect, high drug safety and low risk of hypoglycemia, it can still be considered as an initial drug choice for patients with contraindications to taking metformin.
Bibliography:
Amir Qaseem, Adam J. Obley, Tatyana Shamliyan, et al; Clinical Guidelines Committee of the American College of Physicians. Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. Ann Intern Med. [Epub 19 April 2024].