Dulaglutide/ja

医薬品 > 糖尿病治療薬 > GLP-1受容体作動薬 > Dulaglutide/ja

Dulaglutide/ja

Clinical data
Trade names	Trulicity, others
AHFS/Drugs.com	Monograph
MedlinePlus	a614047
License data	US DailyMed: Dulaglutide
Pregnancy category	AU: B3
Routes of administration	Subcutaneous
Drug class	Incretin mimetic/ja
ATC code	A10BJ05 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only EU: Rx-only
Identifiers
CAS Number	923950-08-7
IUPHAR/BPS	7638
DrugBank	DB09045
UNII	WTT295HSY5
KEGG	D09889
ChEMBL	ChEMBL2108027
Chemical and physical data
Formula	C2646H4044N704O836S18
Molar mass	59670.63 g·mol−1

デュラグルチド（Dulaglutide）は、特にトルリシティ(Trulicity)というブランド名で販売されており、2型糖尿病の治療に用いられる医薬品で、食事療法と運動療法を併用する。また、米国では、確立した心血管疾患または複数の心血管危険因子を有する成人の2型糖尿病患者における主要有害心血管イベントの抑制を適応として承認されている。週1回の注射である。

最も一般的な副作用は、吐き気、下痢、嘔吐、腹痛、食欲低下である。

本薬は、GLP-1(7-37)をヒトIgG4のFcフラグメントと共有結合させたグルカゴン様ペプチド-1受容体作動薬（GLP-1作動薬）である。GLP-1は、血中グルコース濃度（血糖値）の正常化に関与するホルモンである。米国では2014年9月に食品医薬品局（FDA）がデュラグルチドの使用を承認した。欧州連合（EU）では2014年11月に使用が承認された。2021年には、9 万以上の処方で、米国で70番目に多く処方された医薬品であった。

Medical uses

The compound is indicated for adults with type 2 diabetes as an adjunct to diet and exercise to improve glycemic control. Dulaglutide is not indicated in the treatment of subjects with type 1 diabetes or patients with diabetic ketoacidosis because these problems are the result of the islet cells being unable to produce insulin and one of the actions of dulaglutide is to stimulate functioning islet cells to produce more insulin. Dulaglutide can be used either stand-alone or in combination with other medicines for type 2 diabetes, in particular metformin, sulfonylureas, thiazolidinediones, and insulin taken concomitantly with meals.

The medication's phase 3 clinical trial program demonstrated reductions in hemoglobin A1c of approximately 1% with the 0.75 mg and 1.5 mg doses of the medication, along with approximately 5 pounds of weight loss on average. The higher 3.0 mg and 4.5 mg doses that were approved in 2020 demonstrated hemoglobin A1c reductions closer to 1.5% and slightly more weight loss.

A 2017 meta-analysis did not support the suggestion that treatment with GLP-1 agonists or DPP-4 inhibitors increased all-cause mortality in type 2 diabetics.

Side effects

The most common side effects include gastrointestinal disorders, such as dyspepsia, decreased appetite, nausea, vomiting, abdominal pain, diarrhea. Some patients may experience serious adverse reactions: acute pancreatitis (symptoms include persistent severe abdominal pain, sometimes radiating to the back and accompanied by vomiting), hypoglycemia, renal impairment (which may sometimes require hemodialysis). The risk of hypoglycemia is increased if the drug is used in combination with sulfonylureas or insulin. There is also a potential risk of medullary thyroid carcinoma associated with the use of the drug.

Contraindications

The compound is contraindicated in subjects with hypersensitivity to the active ingredient or any of the product's components.

People with a personal or family history of medullary thyroid cancer (MTC) or affected by multiple endocrine neoplasia type 2 should not take dulaglutide, because it could increase the risk of these cancers.

Mechanism of action

Dulaglutide binds to glucagon-like peptide 1 receptors, slowing gastric emptying and increases insulin secretion by pancreatic Beta cells. Simultaneously the compound reduces the elevated glucagon secretion by inhibiting alpha cells of the pancreas, as glucagon is known to be inappropriately elevated in diabetic patients. GLP-1 is normally secreted by L cells of the gastrointestinal mucosa in response to a meal.

History

The safety and effectiveness of dulaglutide were evaluated in six clinical trials in which 3,342 subjects with type 2 diabetes received dulaglutide. Subjects receiving dulaglutide had an improvement in their blood sugar control as observed with reductions in HbA1c level (hemoglobin A1c is a measure of blood sugar control).

The U.S. Food and Drug Administration (FDA) approved dulaglutide with a Risk Evaluation and Mitigation Strategy (REMS), and granted the approval of Trulicity to Eli Lilly and Company. The REMS consists of a number of steps that Eli Lilly will take to make physicians aware of the risk of pancreatitis and the potential risk of medullary thyroid carcinoma associated with the drug.

In 2020, the FDA approved two higher doses of the medication, 3.0 mg and 4.5 mg, based on results of the AWARD-11 trial demonstrating improved glucose lowering and weight benefits.

Further reading

• Scott LJ (February 2020). "Dulaglutide: A Review in Type 2 Diabetes". Drugs. 80 (2): 197–208. doi:10.1007/s40265-020-01260-9. PMID 32002850. S2CID 210954338.
• Edwards KL, Minze MG (2015). "Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes". Core Evidence. 10: 11–21. doi:10.2147/CE.S55944. PMC 4295897. PMID 25657615.
• Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J (February 2019). "A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes". Diabetes Therapy. 10 (1): 5–19. doi:10.1007/s13300-018-0535-9. PMC 6349277. PMID 30506340.