Metformin is no stranger to many sugar friends.
But the compound preparation of metformin, do you understand?
Metformin, as a basic drug for the treatment of type 2 diabetes, is often used in combination with other hypoglycemic drugs. However, taking a variety of hypoglycemic drugs at the same time, patients' compliance is not good, and cases of taking less or missing doses often occur.
Therefore, metformin-based fixed compound preparations have become an important choice for combination therapy.
What are these combinations? What are the advantages in terms of efficacy and safety? Who is it suitable for?
This article will introduce them one by one.
This article invites special review experts:
01
Thiazolidinediones/metformin
Advantages of the formulation:
(1) Both components of the preparation have insulin sensitization effect, which works synergistically to further improve insulin resistance and protect pancreatic islet function.
(2) Independently of hypoglycemia, synergistically improve blood lipids, and comprehensively regulate cholesterol, triglycerides, low-density lipoprotein cholesterol and free fatty acid levels.
Suitable for:
In addition to the ingredients in the preparation with poor single effect, it is mainly suitable for:
(1) Patients with obvious insulin resistance.
(2) Patients with dyslipidemia, simple non-alcoholic fatty liver disease, and polycystic ovary syndrome.
Specific varieties and usage
| variety | specification | The recommended starting dose | Maximum daily dose |
| Pioglitazone metformin tablets | 15 mg/500 mg or 15 mg/850 mg | Take 15 mg/500 mg once in the morning | 45 mg/2550 mg |
| Metformin rosiglitazone maleate tablets | 500 mg/2 mg | Take 500 mg/2 mg once in the morning and evening | 2000 mg/8 mg |
02
Metformin/sulfonylureas
Advantages of the formulation:
Metformin improves insulin resistance, sulfonylureas promote insulin secretion, and the combination is used to complement each other's mechanisms, which can more comprehensively target the different pathogenesis of type 2 diabetes.
Suitable for:
(1) Young, newly diagnosed non-obese type 2 diabetic patients with high glycosylated hemoglobin and good islet function.
(2) Patients who do not respond well to sulfonylurea treatment alone.
Specific varieties and usage
| variety | specification | The recommended starting dose | Maximum daily dose |
| Metformin glibenclamide tablets/capsules | 500 mg/2.5 mg or 250 mg/1.25 mg or 250 mg/2.5 mg | (1) Initial treatment: 250 mg/1.25 mg in the morning; (2) If glycosylated hemoglobin >9%: take 250 mg/1.25 mg once in the morning and evening; (3) Change this product from other drugs: take 500 mg/2.5 mg once in the morning and evening | 2000 mg/10 mg |
| Metformin glipizide tablets/capsules | 500 mg/2.5 mg or 250 mg/2.5 mg | (1) Initial treatment: 250 mg/2.5 mg in the morning; ②若空腹血糖>15.6mmol/L：早晚各服500毫克/2.5毫克1次 | 2000 mg/10 mg |
03
Glinide/metformin
Advantages of the formulation:
(1) Glinide insulin secretion has a short duration of effect, is a prandial blood glucose regulator, combined with metformin, the mechanism of action is complementary, and the fasting and postprandial blood glucose are controlled at the same time.
(2) The hypoglycemic intensity was similar to that of metformin/sulfonylureas, but the risk of hypoglycemia was lower.
Suitable for:
(1) Those who have irregular diet and high blood sugar after meals.
(2) Those who do not have a good effect on the ingredients in this preparation alone or those who have a higher risk of hypoglycemia after the use of metformin/sulfonylureas.
Specific varieties and usage
| variety | specification | The recommended starting dose | Maximum daily dose |
| Regaglinide metformin tablets | 1 mg/500 mg or 2 mg/500 mg | (1) Poor efficacy of metformin alone: take 1 mg/500 mg before meals, 2 times a day; (2) Repaglinide alone is not effective: take 2 mg/500 mg before meals, twice a day | 8 mg/2000 mg |
04
Dipeptidyl peptidase IV. inhibitor (DPP4i)/metformin
Advantages of the formulation:
(1) DPP4i in the preparation component can increase the level of glucagon-like peptide (GLP-1), enhance insulin secretion and inhibit glucagon secretion in a glucose concentration-dependent manner, which is complementary to the metformin mechanism, and the combination can take into account the control of fasting blood glucose and postprandial blood glucose.
(2) Neither component increased the risk of hypoglycemia, and the patients had few gastrointestinal adverse reactions and were well tolerated.
Suitable for:
Initial or replacement therapy for older patients, patients prone to hypoglycemia, and patients with significant gastrointestinal reactions, such as those who are prone to hypoglycemia and those who have significant gastrointestinal reactions.
Specific varieties and usage
| variety | specification | The recommended starting dose | Maximum daily dose |
| Sitagliptin metformin tablets | 50 mg/500 mg or 50 mg/850 mg or 50 mg/1000 mg | Take 50 mg/500 mg or 50 mg/850 mg 2 times daily with meals | 100 mg/2000 mg |
| Sitagliptin metformin extended-release tablets | 50 mg/500 mg or 50 mg/1000 mg or 100 mg/1000 mg | (1) Those who have not taken metformin: take 100 mg/1000 mg with food, once a day; (1) Those who have taken metformin: take 2 tablets of 50 mg/1000 mg with food, once a day | 100 mg/2000 mg |
| Liagliptin metformin tablets | 2.5 mg/500 mg or 2.5 mg/850 mg or 2.5 mg/1000 mg | According to the current dose of metformin, choose the appropriate size and take 1 tablet with food, 2 times a day | 5 mg/2000 mg |
| Saxagliptin metformin extended-release tablets | 2.5 mg/1000 mg or 5 mg/500 mg or 5 mg/1000 mg | Depending on the current treatment regimen, choose a size of 5 mg/500 mg or 2.5 mg/1000 mg and take 1 tablet with a meal, once daily | 5 mg/2000 mg |
| Metformin vildagliptin tablets | 1000 mg/50 mg or 850 mg/50 mg | According to the current dose of metformin, choose the appropriate size and take 1 tablet with food, 2 times a day | 2000 mg/100 mg |
05
Sodium-glucose cotransporter 2 inhibitor (SGLT2i)/metformin
Advantages of the formulation:
(1) SGLT2i promotes urinary glucose excretion by inhibiting glucose reabsorption in renal tubules, and its hypoglycemic effect does not depend on insulin activity, and complements the metformin mechanism to synergistically lower glucose.
(2) SGLT2i has multiple effects of weight loss, blood pressure, lipid regulation and uric acid lowering, and synergistically reduces patients' body weight with metformin, and exerts cardiovascular and renal protective effects.
Suitable for:
In addition to the ingredients in the preparation with poor single effect, it is mainly suitable for:
(1) Overweight or obese patients;
(2) Patients with hypertension, atherosclerotic cardiovascular disease, chronic kidney disease and heart failure.
Specific varieties and usage
| variety | specification | The recommended starting dose | Maximum daily dose |
| Metformin empagliflozin tablets | 500 mg/5 mg or 850 mg/5 mg or 1000 mg/12.5 mg | Depending on the current treatment regimen, choose a size of 500 mg/5 mg or 850 mg/5 mg, taking 1 tablet with food, 2 times daily | 2000 mg/25 mg |
| Dapagliflozin metformin extended-release tablets | 5 mg/500 mg or 5 mg/1000 mg or 10 mg/500 mg or 10 mg/1000 mg or 2.5 mg/1000 mg | Depending on the patient's risk of heart failure and the current therapeutic dose of metformin, select the appropriate size and take it once a day with a meal | 10 mg/2000 mg |
Finally, a reminder to everyone
1. Metformin-based fixed compound preparation is not only used as a second-line replacement drug after the single ingredient in the compound is ineffective, but also can make the blood glucose target as soon as possible, prolong the effective blood sugar control time, delay the progression of type 2 diabetes, and improve the prognosis of patients.
2. There is a possibility of superposition of the contraindications of the two components in the compound preparation, and it is not suitable to use it when there are contraindications for any of the components in the compound.
3. Switching from immediate-release preparations to sustained-release preparations should be closely monitored for blood glucose control and dose adjustments should be made accordingly.
Author: Wei Guo, Chief Pharmacist, Department of Pharmacy, First Affiliated Hospital of Air Force Military Medical University
Bibliography:
[1] Expert Consensus on Metformin-based Fixed Compound Preparations for the Treatment of Type 2 Diabetes Mellitus. Expert consensus on metformin-based fixed compound preparations for the treatment of type 2 diabetes mellitus[J]. Chinese Journal of Diabetes Mellitus, 2022, 14(12):1380-1386.
[2] Chinese Society of Endocrinology. Expert consensus on the combination of oral hypoglycemic drugs for adults with type 2 diabetes mellitus in China[J]. Chinese Journal of Endocrinology and Metabolism, 2019, 3:190-199.
[3] Expert Consensus on the Clinical Application of Metformin Updated Expert Group. Expert consensus on the clinical application of metformin (2023 edition)[J]. China Interior