Pharmacologic Therapy for Type 2 Diabetes
2021:
9.4 Metformin 是治療 2 型糖尿病的首選初始藥物。 A
9.4 Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes. A
2022:
9.4a 第一線治療取決於合併症、以患者為中心的治療因素和管理需求，通常包括 metformin 和全面的生活方式改變 A
9.4a First-line therapy depends on comorbidities, patient-centered treatment factors, and management needs and generally includes metformin and comprehensive lifestyle modification. A
2022 新增
9.4b GLP-1RA、SGLT2i，根據血糖需要可加或不加上metformin，是第二型糖尿病合併動脈硬化心血管疾病、心衰竭和/或慢性腎病的高危險人群合適的初始治療 A
9.4b Other medications (glucagon-like peptide 1 receptor agonists, sodium–glucose cotransporter 2 inhibitors), with or without metformin based on glycemic needs, are appropriate initial therapy for individuals with type 2 diabetes with or at high risk for atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease (Fig. 9.3). A
2021：
一旦開始使用 metformin，只要可以耐受且無禁忌，就應繼續使用； 應在metformin加入其他藥物，包括胰島素 A
9.5 Once initiated, metformin should be continued as long as it is tolerated and not contraindicated; other agents, including insulin, should be added to metformin. A
2022 修正：
9.5 胰島素治療開始後應繼續使用 metformin（除非有禁忌或不耐受），以獲得持續的血糖和代謝益處。 A
9.5 Metformin should be continued upon initiation of insulin therapy (unless contraindicated or not tolerated) for ongoing glycemic and metabolic benefits. A
2021 vs 2022:
9.8 以患者為中心的方法應指導藥物的選擇。 考慮因素包括對心血管和腎臟合併症的影響、療效、低血糖風險、對體重、成本和獲取（2022 年新增）、副作用風險和患者偏好（表 9.1 和圖 9.1）。 B
9.8 A patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include effect on cardiovascular and renal comorbidities, efficacy, hypoglycemia risk, impact on weight, cost and access (2022 新增), risk for side effects, and patient preferences (Table 9.1 and Fig. 9.1). E
2021 vs 2022：
9.9 在已確定動脈粥樣硬化性心血管疾病或心血管高風險指標、已確定腎臟疾病或心力衰竭的 2 型糖尿病患者中，SGLT2 抑製劑或 GLP-1RA 已證實對心血管疾病有益（表 9.1、表 10.3B、表 10.3C）建議作為降糖方案和綜合心血管風險降低的一部分，獨立於 A1C 並考慮患者特定因素（圖 9.1 和第 10 節）。 A
9.9 Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease or indicators of high cardiovascular risk, established kidney disease, or heart failure, a sodium–glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular disease benefit (Table 9.1, Table 10.3B, Table 10.3C) is recommended as part of the glucose-lowering regimen and comprehensive cardiovascular risk reduction (2022 新增)independent of A1C and in consideration of patient-specific factors (Fig. 9.1 and Section 10). A
2022:
9.11 如果使用胰島素，推薦與 GLP-1 RA 聯合治療，以獲得更好的療效和治療效果的持久性。 A
9.11 If insulin is used, combination therapy with a glucagon-like peptide 1 receptor agonist is recommended for greater efficacy and durability of treatment effect. A
Initial Therapy
2021:
除非有禁忌症，否則應在診斷出 2 型糖尿病時開始使用 Metformin； 對於許多患者來說，這將是單一療法與生活方式的改變相結合。
Metformin should be started at the time type 2 diabetes is diagnosed unless there are contraindications; for many patients this will be monotherapy in combination with lifestyle modifications.
2022:
一線治療取決於合併症、以患者為中心的治療因素和管理需求，但通常包括 metformin 和全面的生活方式調整。 除非有禁忌症，否則應在診斷出 2 型糖尿病時開始藥物治療；
First-line therapy depends on comorbidities, patient-centered treatment factors, and management needs but will generally include metformin and comprehensive lifestyle modification. Pharmacotherapy should be started at the time type 2 diabetes is diagnosed unless there are contraindications;
Combination Therapy
2021:
目前的建議是在 metformin 中逐步添加藥物以將 A1C 維持在目標值。 這樣可以更清楚地評估新藥的正面和負面影響，並降低患者風險和費用（44）； 基於這些因素，在 metformin 中順序添加口服藥物已成為標準治療。
Current recommendations have been to use stepwise addition of medications to metformin to maintain A1C at target. This allows a clearer assessment of the positive and negative effects of new drugs and reduces patient risk and expense (44); based on these factors, sequential addition of oral agents to metformin has been the standard of care.
2022 修正
傳統的建議是在 metformin 中逐步添加藥物以將 A1C 維持在目標值。 這樣做的好處是可以清楚地評估新藥的正面和負面影響，並減少潛在的副作用和費用
Traditional recommendations have been to use stepwise addition of medications to metformin to maintain A1C at target. The advantage of this is to provide a clear assessment of the positive and negative effects of new drugs and reduce potential side effects and expense (52).
2021:
此外，由於大多數口服藥物的絕對有效性很少超過 1%，因此 A1C 水平高於目標值 1.5-2.0% 的患者應考慮初始聯合治療。
Moreover, since the absolute effectiveness of most oral medications rarely exceeds 1%, initial combination therapy should be considered in patients presenting with A1C levels 1.5–2.0% above target.
2022: 修正：
A1C 高於目標值 1.5-2.0% ，應考慮初始聯合治療。 結合降糖療效高或心腎風險保護的藥物（例如 GLP-1 RA、SGLT2 抑製劑）可能允許停用當前可能增加低血糖風險的藥物。 因此，治療強化可能不一定遵循純粹的順序添加治療，而是反映了以患者為中心的治療目標的方向來制定。
Initial combination therapy should be considered in patients presenting with A1C levels 1.5–2.0% above target. Finally, incorporation of high glycemic efficacy therapies or therapies for cardiovascular/renal risk reduction (e.g., GLP-1 RAs, SGLT2 inhibitors) may allow for weaning of the current regimen, particularly of agents that may increase the risk of hypoglycemia. Thus, treatment intensification may not necessarily follow a pure sequential addition of therapy but instead reflect a tailoring of the regimen in alignment with patient-centered treatment goals (Fig. 9.3).
2021 vs 2022:
一項比較有效性薈萃分析表明，在 metformin 初始治療中添加的每一類新的非胰島素藥物通常可使 A1C 降低約 0.7-1.0% (49,50)。
2021:
然而，高成本和耐受性問題是 GLP-1 RA 使用的重要障礙。
However, high costs and tolerability issues are important barriers to GLP-1 RA use.
2022: 修正
在強化胰島素治療的患者中，與單獨使用胰島素強化治療相比，與 GLP-1 RA 的聯合治療已被證明具有更高的血糖治療效果和持久性。 然而，成本和耐受性問題是 GLP-1 RA 使用中的重要考慮因素。
In patients who are intensified to insulin therapy, combination therapy with a GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effect than treatment intensification with insulin alone. (2022 新增）However, cost and tolerability issues are important considerations in GLP-1 RA use.
Cardiovascular Outcomes Trials
2022 新增：
新出現的數據表明，使用這兩類藥物將提供額外的心血管和腎臟結果益處； 因此，可以考慮使用 SGLT2 抑製劑和 GLP-1 RA 的聯合治療來提供與這些藥物類別相關的互補結果益處 (74)。
Emerging data suggest that use of both classes of drugs will provide additional cardiovascular and kidney outcomes benefit; thus, combination therapy with an SGLT2 inhibitor and a GLP-1 RA may be considered to provide the complementary outcomes benefits associated with these classes of medication (74).
Insulin Therapy
2022: 新增：
9.11 如果使用胰島素，推薦與 GLP-1 RA 聯合治療，以獲得更好的療效和持久的治療效果。 A
(9.11 If insulin is used, combination therapy with a glucagon-like peptide 1 receptor agonist is recommended for greater efficacy and durability of treatment effect. A)
2021:
2022: 新增：
此外，批准 Glargine 的後續生物製劑、第一個可互換的甘精胰島素產品和類似胰島素的仿製藥可能會擴大具有成本效益的選擇。
Inhalation insulin:
2022 新增：
使用吸入胰島素可能導致肺功能下降（FEV1減少 )
合併治療：
2021： 一項研究表明，與單獨添加基礎胰島素相比，血糖作用的持久性更高（47） (2021 刪）
2022 新增：
DUAL VIII 隨機對照試驗表明，與單獨添加基礎胰島素相比，GLP-1 RA-胰島素聯合治療的血糖治療效果更持久 (55)。 在選定的個體中，複雜的胰島素方案也可以通過 GLP-1 RA-胰島素聯合治療來簡化 2 型糖尿病 (107)。
相同： 有兩種不同的每日一次、固定雙重組合產品，包含基礎胰島素加 GLP-1 RA： insulin glargine plus lixisenatide (iGlarLixi) and insulin degludec plus liraglutide (IDegLira).