Dr. Ahmed Long-acting diabetes medications can be a beneficial treatment option for individuals with diabetes, as they often reduce the frequency of pill-taking.
However, many of these medications still require concomitant daily administration of other medications, either through oral pills or multiple insulin injections, especially in individuals with poorly controlled diabetes.
For those with early-stage, mild diabetes, long-acting medications may significantly decrease the need for daily medication.
For people suffering from diabetes, stability in blood sugar levels is essential to minimize risks for complexities such as cardiovascular disease, neuropathy, and retinopathy.
Long-acting diabetes medications are now the keystone in managing diabetes because they offer an upper hand in having more control over blood glucose levels and facilitating treatment procedures.
How Long-Acting Diabetes Medications Work?
Long-acting diabetes medications are designed to provide predictable therapeutic effects over an extremely long period and reduce dosing frequency.
They are mainly used in the management of type 1 and type 2 diabetes, with the main focus being to control the blood glucose level after fasting.
These medications generally fall into two categories: long-acting insulins and non-insulin therapies, such as GLP-1 receptor agonists.
Long-Acting Insulins
Long-acting insulins mimic the body’s own basal insulin secretion by providing a steady release over several hours. These include:
- Insulin Glargine (Lantus, Toujeo, Basaglar):
- Insulin Glargine is a commonly prescribed long-acting insulin. It provides a steady glucose-lowering activity over 24 hours with minimal risk for peaks and troughs in insulin levels. Available in several formulations, Toujeo’s ultra-long-acting profile may last up to 36 hours.
- Insulin Detemir:
- Insulin detemir has a binding affinity to the albumin in the circulation, allowing its slow release. Its duration of action is generally 16 to 24 hours, and it’s often administered once or twice daily.
- Insulin degludec (Tresiba):
- Insulin degludec is an ultra-long-acting insulin with a duration of action greater than 42 hours. Due to its extended duration, this insulin allows flexibility in dosing time and is a perfect drug of choice for those whose times for food uptake can’t be anticipated.
Mechanism of Action
After injection, long-acting insulins work by either binding to albumin or by creating micro-precipitates.
This helps in slow absorption into the bloodstream. By mimicking the basal secretion of insulin from the pancreas, they maintain stable glucose levels.
Advantages of Long-Acting Insulins
- Simplified Dosing:
- The majority of the long-acting insulins only need once-daily injections that help enhance patient compliance.
- Reduced risk of hypoglycemia:
- The risk of nocturnal hypoglycemia with long-acting insulins is less common when compared to intermediate-action ones like NPH.
- Smoother Glucose Control:
- Since these medications maintain a steady insulin level, they effectively manage fasting blood glucose levels.
Considerations and Side Effects
Long-acting insulins are effective, but they may also have side effects, such as the following:
- Hypoglycemia is less likely to occur, but it is not impossible.
- Reactions at the injection site.
- The patient and health professional must closely monitor weight gain, dosage, and any other concerns.
Insulin Icodec (Once-Weekly Insulin)
Insulin Icodec is an ultra-long-acting insulin, which is very convenient for injection once a week. By maintaining a consistent basal insulin level throughout the week, it has been developed to efficiently control blood sugar levels diabetes patients. This insulin offers an extended duration of action compared to daily long-acting insulins.
Benefits
- Once a Week Dosage: It is convenient for the patient who would have difficulty remembering or managing their daily injections.
- Stable Control of Glucose: It provides a stable amount of insulin for an extended period, which could minimize the variability in blood glucose.
Side Effects
- Risk of hypoglycemia, especially when paired with other insulin or diabetes medications.
- Reactions at injection site.
- Weight gain in some patients.
Non-Insulin Long-Acting Medications
Various pharmacological treatment approaches have been developed to improve diabetic control. Long-acting non-insulin medications work by different physiological pathways.
They include glucagon-like peptide-1 receptor agonists, inhibitors of SGLT2, and DDP-4 inhibitors.
GLP – 1 Receptor Agonist
GLP-1 receptor agonists are injectable medicines that belong to the glucagon-like peptide-1 receptor agonists, these drugs mimic the action of the GLP-1 hormone.
They enhance the secretion of insulin, reduce glucagon levels, and slow gastric motility, leading to a favorable effect on blood sugar control and subsequent weight loss.
Long-Acting Options
- Dulaglutide (Trulicity):
- Administered once weekly, it has a very long half-life and thus can be easier for those patients who may not be as compliant with a daily injection.
- Semaglutide (Ozempic, Rybelsus):
- This medicine is available both as a once-weekly injection (Ozempic) and a once-daily oral tablet (Rybelsus); that is known for its benefit in glycemic control, helping with weight management.
- Exenatide Extended-Release (Bydureon):
- This once-weekly formulation provides extended GLP-1 receptor activation, offering stable glucose control.
Mechanism of Action of GLP-1 Analogs:
GLP-1 receptor agonists stimulate insulin release in a glucose-dependent way, meaning they activate only when blood sugar levels are high.
This minimizes the risk of hypoglycemia and is considered to be one of the significant advantages over some insulin therapies.
Advantages
- Weight Loss:
- Many of these medications are associated with weight loss, an excellent advantage for diabetes type 2 patients because of their obesity problem.
- Cardiovascular Benefit:
- Some GLP-1 receptor agonists have been shown to reduce cardiovascular risk in diabetic patients. These include Liraglutide and Semaglutide.
- Convenience:
- The availability for use in a weekly manner increases adherence compared to other daily drugs.
Adverse Effects
Common adverse effects include nausea, vomiting, and diarrhea, which often decrease as the body becomes accustomed to the medication. Pancreatitis and thyroid tumors rarely occur.
SGLT2 Inhibitors
Although not considered long-acting by definition, sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), enable once-daily dosing that simplifies the management of diabetes.
By stimulating the excretion of glucose through urine these drugs work to help lower blood glucose.
Benefits
- Kidney and Heart Protection:
- SGLT2 inhibitors slow the progression of kidney disease and heart failure in diabetes patients.
- Weight Reduction:
- Glucose excretion promotes caloric loss and thus supports good weight management.
Side Effects
These drugs may cause:
- Urinary tract infections (UTIs).
- Genital yeast infections.
- Dehydration.
Patients should ensure adequate hydration and monitor for signs of infection.
Trelagliptin (Once-Weekly DPP-IV Inhibitor)
Trelagliptin is a once-weekly medication that functions as a DPP-IV (dipeptidyl peptidase-4) inhibitor. DPP-IV inhibitors enhance insulin secretion and reduce glucagon levels in a glucose-dependent manner, which reduces blood glucose levels.
Trelagliptin has a long half-life that allows it to be administered once weekly, making it a good option for patients who cannot tolerate daily medications.
Benefits
- Convenient Weekly Dosing:
- This once-weekly formulation is good for patients who have adherence problems.
- Cardiovascular Benefits:
- There is a suggestion that DPP-IV inhibitors might have beneficial effects on cardiovascular outcomes in diabetes patients.
Side Effects
- Mild digestive disturbances such as nausea or diarrhea.
- Rare risk of pancreatitis.
Comparing Long-Acting Options
When choosing a medication to treat diabetes that has a prolonged action or duration, the following factors should be carefully considered:
Cost
Long-acting insulins and newer GLP-1 receptor agonists are expensive. Medication choice may also be influenced by insurance coverage and patient assistance programs.
Efficacy
Long-acting insulins are very effective for maintaining control of fasting glucose. Whereas GLP-1 receptor agonists provide full-spectrum control and have extra benefits, including weight loss and cardiovascular protection.
Convenience
Once-weekly injectable GLP-1 receptor agonists offer convenience for patients who cannot tolerate daily injections, whereas generally, the long-acting insulins need to be given once daily.
Side Effect Profile
Gastrointestinal side effects are common with GLP-1 receptor agonists but carry a lower risk of hypoglycemia. Weight gain and hypoglycemia—with particular risk if dosed incorrectly—are potential side effects of long-acting insulins.
In Summary:
Long-acting diabetes medications are designed to provide consistent blood sugar control over an extended period. This can help reduce the frequency of injections or pill-taking compared to shorter-acting medications.
Here are some common types of long-acting diabetes medications:
- Long-acting insulin: These are injectable medications that provide a steady level of insulin throughout the day.
- GLP-1 receptor agonists: These medications mimic a natural hormone that helps regulate blood sugar. They are typically injected once weekly.
- DPP-IV Inhibitors: Most DPP-IV Inhibitors are administered once daily. However, Trelagliptin is administered once every week.
