Ten questions and ten answers: One article to grasp the clinical application of DPP-4i

Edited by Yimaitong, please do not reprint without authorization
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Dipeptidyl peptidase 4 inhibitor (DPP-4i) is a new type of hypoglycemic drug that has been marketed in recent years.
Combined with the newly released "Expert Guidance and Suggestions on Common Problems in Clinical Application of Dipeptidyl Peptidase 4 Inhibitor in Primary Medical Institutions", This article summarizes ten problems that may be encountered in the clinical use of DPP-4i for teachers' reference
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Question 1: The hypoglycemic mechanism of DPP-4i? DPP-4i lowers blood sugar mainly by inhibiting the activity of DPP-4, reducing the inactivation of GLP-1 in vivo, and increasing the intensity and duration of action of endogenous GLP-1 within the physiological concentration range
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Note: DPP-4 is a cell surface serine protease, which can rapidly degrade human endogenous GLP-1 and lose its activity, resulting in a weakened incretin effect and increased blood sugar
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GLP-1 promotes the secretion of Ins from islet β cells in a glucose concentration-dependent manner, while inhibiting the secretion of glucagon from islet α cells, thereby exerting a hypoglycemic effect
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Question 2: Dosage and usage precautions? Currently, a total of 5 DPP-4i preparations have been approved for clinical treatment of T2DM in China (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin).
The usage and dosage are shown in the table.
1
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Table 1 DPP-4i usage and dosage Notes: ➤It is recommended to take it at a relatively fixed time of day with or without meals; ➤Vildagliptin is administered once in the morning and once in the evening, combined with sulfonylureas (SU) It is recommended to take 50mg, qd, in the morning; ➤ Saxagliptin should not be taken apart
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Question 3: What drugs can DPP-4i be used in combination with? Chinese guidelines recommend that DPP-4i can be used alone or in combination with metformin, α-glucosidase inhibitors, SU, thiazolidinediones (TZDs), SGLT2i and insulin
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DPP-4i is not recommended for use with GLP-1RA
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However, it should be noted that the approved combination drugs in the instructions only involve metformin, sulfonylureas, and insulin (see Table 2).
and signed the informed consent
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Table 2 Approved combination drugs in the current label When used in combination with other oral hypoglycemic agents: ➤DPP-4i in combination with metformin, alpha-glucosidase inhibitor, SU, TZD or SGLT2i can further improve glycemic control and is significantly better than single drug treatment
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➤Combined use of SU: When DPP-4i is combined with SU, attention should be paid to the risk of hypoglycemia, and the dose of SU should be appropriately reduced; ➤Combined use of metformin: Compared with SU, it has advantages in terms of hypoglycemia risk and weight management; ➤Combined use of acarbo Sugar: Helps to improve islet β-cell function; ➤ Combined with SGLT-2i: further reduces HbA1c, blood pressure, and weight loss
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When used in combination with insulin: ➤ Significantly lowers HbA1c levels and reduces insulin dosage; ➤ Glucose monitoring should be strengthened, and insulin dosage should be adjusted according to blood sugar levels to prevent hypoglycemia; ➤ T2DM patients treated with basal or premixed insulin combined with DPP- 4i, can further reduce HbA1c, fasting blood glucose (FPG), reduce insulin dosage, and the incidence of hypoglycemia and body weight are not different from the combined placebo group
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Question 4: Why does the guideline not recommend the combined use of DPP-4i and GLP-1RA? On this issue, Yimaitong once interviewed Professor Mu Yiming of the People's Liberation Army General Hospital
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Professor Yoshiaki Mu said that the reason is that the drug effects of the two types of drugs overlap
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In theory, it is not absolutely impossible to use the two together, but it is not recommended
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Article link: "Clinical expert consensus on the use of GLP-1 receptor agonists in the treatment of type 2 diabetes" released! Question 5: What are the common usage scenarios of DPP-4i? In clinical practice, the common use scenarios of DPP-4i include: 1.
Patients with metformin contraindications or intolerance and elderly T2DM patients can initiate DPP-4i therapy as a single agent
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2.
After metformin monotherapy and adequate dose adjustment for 3 months, patients whose blood glucose control has not yet reached the individualized target, especially those with poor postprandial blood glucose (PPG) control, can be treated with DPP-4i
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3.
For patients who cannot tolerate high-dose (≥2000 mg/d) metformin monotherapy due to gastrointestinal reactions, low-dose (≤1000 mg/d) metformin combined with DPP-4i therapy can be considered
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4.
When adverse reactions (such as hypoglycemia, significant weight gain) occur in combination therapy with other hypoglycemic drugs, it may be considered to change the drugs that cause hypoglycemia or weight gain to DPP-4i
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5.
For newly diagnosed T2DM patients treated with short-term intensive insulin therapy, some patients can be changed to DPP-4i monotherapy or combined with metformin after hyperglycemia is controlled or relieved
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6.
For newly diagnosed T2DM patients with baseline HbA1c≥7.
5%, DPP-4i can be used as one of the hypoglycemic drug options for initial combined therapy
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Question 6: How to adjust the dose for patients with hepatic and renal insufficiency? Before starting DPP-4i treatment, evaluate the patient's liver and kidney function, and periodically after starting treatment.
The dosage adjustment plan for patients with liver and kidney insufficiency is shown in Table 3
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Table 3 Application of DPP-4i in patients with hepatic and renal insufficiency Question 7: When the conditions are insufficient to evaluate the patient's hepatic and renal function? ➤ Linagliptin can be used in patients with hepatic and renal insufficiency throughout the course without dose adjustment; ➤ Saxagliptin does not require dose adjustment in patients with hepatic insufficiency
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Question 8: Application of DPP-4i in the elderly For elderly patients with T2DM over 65 years old: ➤ DPP-4i can be used alone or in combination with other hypoglycemic drugs, without additional risk of hypoglycemia and weight, easy to use, It is a more suitable hypoglycemic treatment plan; ➤The use of sitagliptin and saxagliptin has good efficacy and tolerability, and the incidence of adverse reactions is similar to the overall population; ➤In patients with further CVD or DKD, Liger Liptin can effectively improve blood sugar without increasing the risk of adverse cardio-renal events
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Question 9: The adverse reactions of DPP-4i and the overall safety of DPP-4i treatment are good, and adverse reactions are relatively rare: ➤ Gastrointestinal manifestations: The main manifestations are nausea, vomiting and diarrhea, but the symptoms are generally mild and short in duration , no special handling is required
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➤Respiratory system manifestations: including nasopharyngitis, headache, upper respiratory tract infection, etc.
Among them, nasopharyngitis can be manifested as nasal congestion, runny nose, throat pain and discomfort, cough, wheezing and fatigue, and most of the symptoms subside after 3 days of drug withdrawal.
A report of allergic rhinitis
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➤Other: If pancreatitis, severe allergic or hypersensitivity reactions are suspected, the drug should be discontinued immediately
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Question 10: Who is prohibited from using DPP-4i? ➤Those who are known to be allergic to the drug or any component in the drug, such as anaphylaxis, angioedema, exfoliative skin lesions, bronchial hypersensitivity, etc.
; ➤Not recommended for type 1 diabetes, children and adolescents under 18 with T2DM, Patients with DKA, pregnancy and lactation, with a history of pancreatitis or at high risk; ➤Saxagliptin or alogliptin should be used with caution in T2DM patients with predisposing factors for heart failure
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Vildagliptin is not recommended for patients with New York Heart Association functional class IV; ➤ Saxagliptin and vildagliptin contain lactose, rare genetic diseases of galactose intolerance, Lapp lactase deficiency, or glucose - Contraindicated in patients with galactose malabsorption
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Reference: Neurology and Endocrinology Group, Endocrinology Branch of Chinese Medical Association.
Expert guidance and advice on common problems in clinical application of dipeptidyl peptidase 4 inhibitors in primary medical institutions.
Chinese Journal of Diabetes.
2022