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Table 9.2 —Medications for lowering glucose, summary of characteristics\n Dual\nCV, cardiovascular; CVOT, cardiovascular outcomes trial; DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; GI, gas- | [
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0.010832... |
trointestinal; GIP, glucose-dependent insulinotropic polypeptide; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; NASH, nonalcoholic steatohepatitis; MACE, major adverse car- | [
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diovascular events; SGLT2, sodium–glucose cotransporter 2; SQ, subcutaneous; T2DM, type 2 diabetes mellitus. *For agent-speci fic dosing recommendations, please refer to manufacturers ’ | [
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prescribing information.1Tsapas et al. (104).2Tsapas et al. (152). Adapted from Davies et al. (84).diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S167\n©AmericanDiabetesAssociation | [
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oral therapy, and combination injectable\ntherapy. Weight management is a distincttreatment goal, along with glycemic man-agement, in individuals with type 2 dia-betes, as it has multifaceted bene fits, in- | [
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cluding improved glycemic management,reduction in hepatic steatosis, and im-provement in cardiovascular risk factors(84–86). The glucose-lowering treatment\nplan should therefore consider approachesthat support weight management goals,with semaglutide and tirzepatide cur-rently having the highest weight loss ef fi- | [
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cacy among agents approved for glycemicmanagement ( Fig. 9.3 and Table 9.2 )\n(84,87,88). Additional weight manage-ment approaches, alone or in combina-tion, should be used if needed to achieve\nindividual goals (i.e., intensive behavioral\nmanagement programs, weight loss phar-macotherapies, or metabolic surgery).See ... | [
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Management, ”for approaches to achieve\nweight management goals.\nMetformin is effective and safe, is in-\nexpensive and widely available, and mayreduce risk of cardiovascular events and\ndeath (89). Metformin is available in an\nimmediate-release form for twice-dailydosing or as an extended-release formthat can be giv... | [
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with sulfonylureas, metformin as first-\nline therapy has bene ficial effects on\nA1C, is weight neutral, does not cause\nhypoglycemia, and reduces cardiovascu-lar mortality (90).\nThe principal side effects of metformin | [
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The principal side effects of metformin\nare gastrointestinal intolerance due tobloating, abdominal discomfort, and diar-rhea; these can be mitigated by gradualdose titration and/or using extended-\nrelease formulation. The drug is cleared\nby renal filtration, and very high circulat- | [
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by renal filtration, and very high circulat-\ning levels (e.g., as a result of overdose oracute renal failure) have been associated\nwith lactic acidosis. However, the occur-\nrence of this complication is now knownto be very rare, and metformin may besafely used in people with estimated glo-\nmerular filtration rate $30... | [
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merular filtration rate $30 mL/min/1.73 m\n2\n(91). A randomized trial con firmed previ-\nous observations that metformin use is\nassociated with vitamin B12 de ficiency\nand worsening of symptoms of neuropa-\nthy (92). This is compatible with a report | [
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thy (92). This is compatible with a report\nfrom the Diabetes Prevention ProgramOutcomes Study (DPPOS) suggesting peri-odic testing of vitamin B12 levels (93)\n(see Section 3, “Prevention or Delay of\nDiabetes and Associated Comorbidities ”)in individuals treated with metformin for\nan extended period of time.\nWhen A1... | [
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an extended period of time.\nWhen A1C is $1.5% above the indi-\nvidualized glycemic goal (see Section 6,\n“Glycemic Goals and Hypoglycemia, ”for\nappropriate goals), many individuals willrequire dual-combination therapy or amore potent glucose-lowering agent to\nachieve and maintain their goal A1C level\n(84,94) ( Fig.... | [
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(84,94) ( Fig. 9.3 andTable 9.2 ). Insulin has\nthe advantage of being effective whereother agents are not and should be consid-ered as part of any combination medica-\ntion plan when hyperglycemia is severe, | [
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tion plan when hyperglycemia is severe,\nespecially if catabolic features (weight loss,hypertriglyceridemia, ketosis) are present.It is common practice to initiate insulintherapy for people who present withblood glucose levels $300 mg/dL ( $16.7\nmmol/L) or A1C >10% (>86 mmol/mol) | [
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mmol/L) or A1C >10% (>86 mmol/mol)\nor if the individual has symptoms of hyper-glycemia (i.e., polyuria or polydipsia) or ev-idence of catabolism (unexpected weightloss) ( Fig. 9.4). As glucose toxicity resolves, | [
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simplifying the medication plan and/orchanging to noninsulin agents is often pos-sible. However, there is evidence that peo-ple with poorly managed hyperglycemiaassociated with type 2 diabetes can alsobe effectively treated with a sulfonylurea,\nGLP-1 RA, or dual GIP and GLP-1 RA | [
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GLP-1 RA, or dual GIP and GLP-1 RA\n(87,88,95). GLP-1 RAs and tirzepatide haveadditional bene fits over insulin and sulfo-\nnylureas, speci fically lower risk for hypogly-\ncemia (both) and favorable weight (both),cardiovascular (GLP-1 RAs), and kidney\n(GLP-1 RAs) end points.\nCombination Therapy\nBecause type 2 diabete... | [
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Combination Therapy\nBecause type 2 diabetes is a progressive\ndisease in many individuals, maintenanceof glycemic goals often requires combina-tion therapy. Traditional recommendationshave been to use stepwise addition of\nmedications to metformin to maintain goal | [
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medications to metformin to maintain goal\nA1C. The advantage of this is to provide aclear assessment of the positive and nega-tive effects of new drugs and reduce po-tential side effects and expense (96).However, there are data to support initial\ncombination therapy for more rapid attain- | [
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combination therapy for more rapid attain-\nment of glycemic goals (97,98) and latercombination therapy for longer durabilityof glycemic effect (99). The VERIFY (Vilda-gliptin Ef ficacy in combination with met-\nformin For earlY treatment of type 2\ndiabetes) trial demonstrated that initial\ncombination therapy —in this... | [
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combination therapy —in this case of met-\nformin and the dipeptidyl peptidase 4(DPP-4) inhibitor vildagliptin —is superior\nto sequential addition of medications for\nextending primary and secondary failure(100). Initial combination therapy shouldbe considered in people presenting with\nA1C levels 1.5 –2.0% above goal... | [
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A1C levels 1.5 –2.0% above goal. Finally,\nincorporation of high-glycemic-ef ficacy\ntherapies or therapies for cardiovascular\nand kidney disease risk reduction (e.g.,\nGLP-1 RAs, dual GIP and GLP-1 RA, and\nSGLT2 inhibitors) may allow for weaning ofthe current medication plan, particularly ofagents that may increase t... | [
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glycemia and weight gain. Thus, treatment\nintensi fication may not necessarily follow a\npure sequential addition of therapy but in-stead re flect a tailoring of the medication\nplan in alignment with person-centered\ntreatment goals and pursuit of multifaceted\ntreatment goals ( Fig. 9.3).\nTreatment intensi fication, d... | [
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Treatment intensi fication, deintensi fica-\ntion, or modi fication —as appropriate— for\npeople not meeting individualized treat-\nment goals should not be delayed. Shared\ndecision-making is important in discussionsregarding treatment change. The choiceof medication added to initial therapy is\nbased on the clinical cha... | [
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based on the clinical characteristics of the\nindividual and their preferences and goalsfor care. Important clinical characteristicsinclude the presence of overweight or obe-\nsity, established ASCVD or indicators of | [
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sity, established ASCVD or indicators of\nhigh ASCVD risk, HF, CKD, obesity, nonalco-holic fatty liver disease or nonalcoholicsteatohepatitis, hypoglycemia, and risk forspecifi c adverse drug effects, as well as | [
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safety, tolerability, accessibility, usability,and cost. Results from comparative effec-tiveness meta-analyses suggest that eachnew class of oral noninsulin agents added\nto initial therapy with metformin gener-\nally lowers A1C approximately 0.7 –1.0%\n(8–11 mmol/mol); if a GLP-1 RA or the\ndual GIP and GLP-1 RA is ad... | [
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dual GIP and GLP-1 RA is added, a 1\nto$2% lowering in A1C is expected\n(87,101,102) ( Fig. 9.3 andTable 9.2 ).\nFor people with type 2 diabetes and\nestablished ASCVD or indicators of high\nASCVD risk, HF, or CKD, an SGLT2 inhibi-\ntor and/or GLP-1 RA with demonstrated\ncardiovascular bene fit (see Table 9.2 , | [
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cardiovascular bene fit (see Table 9.2 ,\nTable 10.3 B,a n d Table 10.3 C)i sr e c o m -\nmended as part of the glucose-loweringplan independent of A1C, independent\nof metformin use, and in consideration\nof person-speci ficf a c t o r s( Fig. 9.3 ). Indi-\nviduals with these comorbidities alreadyachieving their individ... | [
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goals with other medications may bene-\nfit\nfrom switching to these preferredS168 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 47, Supplement 1, January 2024\n©AmericanDiabetesAssociation | [
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medications, if possible, to reduce risk\nof ASCVD, HF, and/or CKD in addition toachieving glycemic goals (see Section10, “Cardiovascular Disease and Risk\nManagement ”and Section 11, “Chronic\nKidney Disease and Risk Management ”).\nThis is particularly important as SGLT2inhibitors and GLP-1 RA are associatedwith lowe... | [
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0.05525147169828415,
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0.008229211904108524,
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0.09974543005228043,
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0.024176152423024178,
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-0.01... |
dividuals with ASCVD, HF, and CKD ex-\nperience heightened hypoglycemia risk.\nFor people without established ASCVD,\nindicators of high ASCVD risk, HF, or CKD,medication choice is guided by ef ficacy in | [
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support of individualized glycemic andweight management goals, avoidance ofside effects (particularly hypoglycemiaand weight gain), cost/access, and individ-\nual preferences (103). A systematic review\nand network meta-analysis suggests thatthe greatest reductions in A1C level arewith insulin plans, speci fic GLP-1 RAs | [
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(particularly semaglutide), and tirzepatide\n(87,88,104). In all cases, treatment plans\nneed to be continuously reviewed for ef fi-\nc a c y ,s i d ee f f e c t s ,a n db u r d e n( Table 9.2 ).\nIn some instances, the individual will re-\nquire medication reduction or discontinu- | [
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quire medication reduction or discontinu-\nation. Common reasons for this includeineffectiveness, hypoglycemia, intolerableside effects, new contraindications, ex-\npense, or a change in glycemic goals (e.g.,\nin response to development of comorbid-ities or changes in treatment goals). Section13,“Older Adults,” has a f... | [
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treatment considerations in older adults, in\nwhom changes of glycemic goals and de-\nescalation of therapy are common.\nThe need for the greater potency of\ninjectable medications is common, par-ticularly in people with a longer dura-\ntion of diabetes. The addition of basal | [
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0.0002... |
tion of diabetes. The addition of basal\ninsulin, either human NPH or one of thelong-acting insulin analogs, to oral agentmedication plans is a well-established\napproach that is effective for many indi-\nviduals. In addition, evidence supportsthe utility of GLP-1 RAs in people not at-taining their glycemic goals. Whil... | [
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0.018... |
GLP-1 RAs are injectable, an oral formu-\nlation of semaglutide is commerciallyavailable (105). In trials comparing theaddition of an injectable GLP-1 RA, dualG I Pa n dG L P - 1R A ,o ri n s u l i ni np e o p l e\nneeding further glucose lowering, glyce-\nmic ef ficacies of injectable GLP-1 RA | [
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mic ef ficacies of injectable GLP-1 RA\nand dual GIP and GLP-1 RA were similarto or greater than that of basal insulin\n(106–113). GLP-1 RAs and dual GIP and\nGLP-1 RA in these trials had a lower riskof hypoglycemia and bene ficial effects\non body weight compared with insulin, | [
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on body weight compared with insulin,\nalbeit with greater gastrointestinal sideeffects. Thus, trial results support highpotency GLP-1 RAs and dual GIP andGLP-1 RA as the preferred options for\nindividuals requiring the potency of an\ninjectable therapy for glucose manage-ment ( Fig. 9.4). In individuals who are in- | [
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tensified to insulin therapy, combination\ntherapy with a GLP-1 RA or a dual GIPand GLP-1 RA has been shown to have\ngreater effi cacy and durability of glycemic\ntreatment effect, as well as weight and\nhypoglycemia bene fit, than treatment in-\ntensification with insulin alone (84,114).\nHowever, cost and tolerability is... | [
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However, cost and tolerability issues are\nimportant considerations in GLP-1 RA and\ndual GIP and GLP-1 RA use.\nCosts for diabetes medications have in-\ncreased dramatically over the past twodecades, and an increasing proportion isnow passed on to people with diabetesand their families (115). Table 9.3 provides | [
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cost information for currently approvednoninsulin therapies. Of note, prices listedare average wholesale prices (AWP) (116)and National Average Drug AcquisitionCosts (NADAC) (117), separate measuresto allow for a comparison of drug prices,\nbut do not account for discounts, rebates, | [
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-0... |
but do not account for discounts, rebates,\nor other price adjustments often involvedin prescription sales that affect the actualcost incurred by the individual. Medicationcosts can be a major source of stress forpeople with diabetes and contribute to\nworse medication-taking behavior (118); | [
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worse medication-taking behavior (118);\ncost-reducing strategies may improve medi-cation-taking behavior in some cases (119).Although caps on costs are starting to occurfor insulin products, no such caps exist for\ndiabetes durable medical equipment or for | [
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diabetes durable medical equipment or for\nnoninsulin medications. It is therefore es-sential to screen all people with diabetesforfinancial concerns and cost-related bar-\nriers to care and to engage members of thehe\nalth care team —including pharmacists,\ncertified diabetes care and education spe- | [
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0.00... |
certified diabetes care and education spe-\ncialists, social workers, community healthworkers, community paramedics, andothers —to identify cost-saving opportuni-\nties for medications, diabetes durable\nmedical equipment, and glucagon (120).\nCardiovascular Outcomes Trials | [
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medical equipment, and glucagon (120).\nCardiovascular Outcomes Trials\nThere are now multiple large randomizedcontrolled trials reporting statistically sig-\nnificant reductions in cardiovascular events\nin adults with type 2 diabetes treatedwith an SGLT2 inhibitor or GLP-1 RA; see\nSection 10, “Cardiovascular Disease ... | [
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-0.0306... |
Section 10, “Cardiovascular Disease and\nRisk Management, ”for details. Partici-\npants enrolled in many of the cardiovas-cular outcomes trials had A1C $6.5%\n($48 mmol/mol), with more than 70%\ntaking metformin at baseline, with analy-ses indicating bene fit with or without met-\nformin (84). Thus, a practical extensio... | [
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formin (84). Thus, a practical extension of\nthese results to clinical practice is to use\nthese medications preferentially in peoplewith type 2 diabetes and establishedASCVD or indicators of high ASCVD risk.\nFor these individuals, incorporating one | [
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0.0376... |
For these individuals, incorporating one\nof the SGLT2 inhibitors and/or GLP-1 RAsthat have been demonstrated to havecardiovascular disease bene fiti sr e c -\nommended (see Fig. 9.3 ,Table 9.2 ,a n d\nSection 10, “Cardiovascular Disease\nand Risk Management ”). Emerging data | [
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0.0... |
and Risk Management ”). Emerging data\nsuggest that use of both classes of drugswill provide additional cardiovascular and\nkidney outcomes bene fit; thus, combina-\ntion therapy with an SGLT2 inhibitor and a\nGLP-1 RA may be considered to providethe complementary outcomes benefi ts as- | [
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sociated with these classes of medication(121). In cardiovascular outcomes trials,empagli flozin, canagli flozin, dapagli flozin,\nliraglutide, semaglutide, and dulaglutide allhad bene ficial effects on indices of CKD,\nwhile dedicated renal outcomes studieshave demonstrated bene fito fs p e c i fic\nSGLT2 inhibitors. See Se... | [
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SGLT2 inhibitors. See Section 11, “Chronic\nKidney Disease and Risk Management,”\nfor discussion of how CKD may impact\ntreatment choices. Additional large ran-domized trials of other agents in theseclasses are ongoing.\nIndividuals at low risk for ASCVD may\nbenefit from GLP-1 RA therapy to reduce | [
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benefit from GLP-1 RA therapy to reduce\ntheir risk of future ASCVD events, althoughthe evidence is currently limited. The Gly-cemia Reduction Approaches in Type 2\nDiabetes: A Comparative Effectiveness | [
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Diabetes: A Comparative Effectiveness\nStudy (GRADE), which was designed toexamine the comparative effectiveness ofinsulin glargine U-100, glimepiride, liraglu-tide, and sitagliptin in individuals with\nshort duration of diabetes with respect to | [
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short duration of diabetes with respect to\nachieving and maintaining glycemic con-trol, found that individuals treated withliraglutide had a slightly lower risk of car-\ndiovascular disease compared with individ-\nuals receiving the other three treatments(hazard ratio 0.7 [95% CI 0.6 –0.9]), al-\nthough no signi ficant... | [
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0.03791085630655289,
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-... |
though no signi ficant differences were\nfound for major adverse cardiovascularevents, hospitalization for HF, or cardiovas-cular death (122).diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S169\n©AmericanDiabetesAssociation | [
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Insulin Therapy\nMany adults with type 2 diabetes even-\ntually require and bene fit from insulin\ntherapy ( Fig. 9.4 ). See the section INSULIN\nADMINISTRATION TECHNIQUE , above, for guid-\nance on how to administer insulin safelyand effectively. The progressive nature\nof type 2 diabetes should be regularlyand objecti... | [
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0.0032... |
with diabetes, and clinicians should\navoid using insulin as a threat or de-scribing it as a sign of personal failure\nor punishment. Rather, the utility and\nimportance of insulin to maintain glyce-mic control once progression of the dis-\nease overcomes the effect of other\nagents should be emphasized. Educat-ing and... | [
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0.011479... |
in insulin management is bene ficial. For\nexample, instruction of individuals with\ntype 2 diabetes initiating insulin in self-titration of insulin doses based on glu-\ncose monitoring improves glycemic\nmanagement (123). Comprehensive ed-ucation regarding blood glucose moni-\ntoring, nutrition, and the avoidance and | [
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toring, nutrition, and the avoidance and\nappropriate treatment of hypoglycemiaare critically important in any individual\nusing insulin.\nBasal Insulin\nBasal insulin alone is the most convenientinitial insulin treatment and can be added\nto metformin and other noninsulin inject-ables for individuals with type 2 diabe... | [
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Starting doses can be estimated based on\nbody weight (0.1 –0.2 units/kg/day) and\nthe degree of hyperglycemia, with indi-\nvidualized titration over days to weeks as\nneeded. The principal action of basal insu-lin is to restrain hepatic glucose produc-tion and limit hyperglycemia overnight\nand between meals (124,125)... | [
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0.0461956225335598,
-0.0151241235435009,
-0.026660142466425896,
0.013... |
and between meals (124,125). Attain-\nment of fasting glucose goals can beachieved with human NPH insulin or a\nlong-acting insulin analog. In clinical trials,\nlong-acting basal analogs (U-100 glargineor detemir) have been demonstrated to\nreduce the risk of level 2 hypoglycemia and | [
-0.012748109176754951,
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0.017880022525787354,
-0.02831573225557804,
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... |
reduce the risk of level 2 hypoglycemia and\nnocturnal hypoglycemia compared withNPH insulin (126). Longer-acting basal ana-\nlogs (U-300 glargine or degludec) convey a\nlower nocturnal hypoglycemia risk com-pared with U-100 glargine (127,128). Clini-cians should be aware of the potential\nfor overbasalization with ins... | [
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-0.06346110254526138,
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0.046135... |
for overbasalization with insulin therapy.\nClinical signals that may prompt evalua-tion of overbasalization include basal\ndose greater than /C240.5 units/kg, high\nbedtime-to-morning or preprandial-to-postprandial glucose differential (e.g.,bedtime-to-morning glucose differential$50 mg/dL [ $2.8 mmol/L]), hypoglyce- | [
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... |
mia (aware or unaware), and high vari-ability. Indication of overbasalization\nshould prompt reevaluation to further in-\ndividualize therapy (129).\nThe cost of insulin has been rising\nsteadily over the past two decades, at apace severalfold that of other medical\nexpenditures. This expense contributes\nsignificant bu... | [
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0.004... |
significant burden to people with diabe-\ntes, as insulin has become a growing“out-of-pocket ”cost for people with di-\nabetes, and direct costs contribute todecrease in medication-taking behavior(130). As of January 2023, the cost ofindividual insulins was capped for en-\nrollees in Medicare Part D plans (131), | [
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... |
rollees in Medicare Part D plans (131),\nand at least 20 states and the District ofColumbia have also capped insulin costsfor enrollees in state-sponsored plansand, in select states, for those without\ninsurance. In 2023, the three major U.S. | [
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0.010837377980351448,
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insurance. In 2023, the three major U.S.\ninsulin manufacturers also announcedplans to reduce insulin prices; someplans go into effect in January 2024,\nand another has already occurred. The\nsummary of the cost of insulin productsinTable 9.4 provides a comparison but\nis not re flective of the Medicare or | [
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-0.0018297930946573615,
0.03998856246471405,
0.04039308428764343,
0.022055208683013916,
0.040607377886772156,
-0.022693578153848648,
0.014414802193641663,
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0.1037885993719101,
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-0.... |
is not re flective of the Medicare or\nstate-level caps or the recent manufac-turer price reductions. However, the in-formation in Table 9.4 reflects how the\napproval of unbranded versions (insulinaspart, lispro, degludec, glargine U-100,\nand some premixed products), follow- | [
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0.004219905938953161,
0.024075321853160858,
0.08927956968545914,
0.08417228609323502,
-0.0694621130824089,
0.0033576665446162224,
0.021267985925078392,
0.055695876479148865,
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-0.05... |
and some premixed products), follow-\non products (insulin lispro and glargine),and interchangeable biosimilars (insulinglargine) have led to lower costs com-\npared with other products. For some in-\ndividuals with type 2 diabetes (e.g.,individuals with relaxed A1C goals, lowrates of hypoglycemia, and prominent | [
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0.01248390693217516,
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0.06257389485836029,
0.14422287046909332,
0.047761932015419006,
0.0011846072738990188,
0.003431758377701044,
0.061411354690790176,
-0.08364959061145782,
-... |
insulin resistance as well as those with\ncost concerns), human insulin (NPH andregular) may be the appropriate choiceof therapy, and clinicians should be fa-miliar with its use (132). Human regular\ninsulin, NPH, and 70/30 NPH/regular | [
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0.03353744000196457,
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0.03418690711259842,
0.08120067417621613,
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-0.01890476979315281,
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0.06... |
insulin, NPH, and 70/30 NPH/regular\nproducts can be purchased for consider-ably less than the AWP and NADAC priceslisted in Table 9.4 at select pharmacies. It\nis important to note that although thesecaps, price reductions, use of unbrandedor biosimilar versions of analogs, or useof human insulins may impact the cost | [
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0.05381406098604202,
0.09218121320009232,
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0.06617143750190735,
-0.0069405315443873405,
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-0.08962041139602661,
0.02... |
of insulin products, there are no caps on\nthe costs of the other tools individualswith diabetes need for monitoring ortreatment (including glucose monitoringsupplies [strips or sensors], administrationtools [pen needles, syringes, and insulinpumps], ketone testing supplies, and glu-cagon). Therefore, routine assessmen... | [
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-0.07591366767883301,
-0.06444036215543747,
... |
financial obstacles that may impact diabe-\ntes management is an important compo-\nnent of effective care of people withdiabetes. Collaboration between mem-\nbers of the health care team and with so-\ncial service professionals to identify andimplement cost reduction strategies tosupport and improve access to evidence- | [
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0.056400883942842484,
0.047872159630060196,
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0.04107289016246796,
-0.023702841252088547,
0.025966444984078407,
-0.019695620983839035,
0.04... |
based care is important (120,130).\nPrandial Insulin\nMany individuals with type 2 diabetes\nrequire doses of insulin before meals, inaddition to basal insulin, to reach glyce-\nmic goals. If an individual is not already\nbeing treated with a GLP-1 RA or dualGIP and GLP-1 RA, a GLP-1 RA (either asan individual product ... | [
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0.020069513469934464,
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0.07773247361183167,
0.07050377875566483,
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-0.02... |
combination with a basal insulin prod-uct) or dual GIP and GLP-1 RA should beconsidered prior to prandial insulin tofurther address prandial control and to\nminimize the risks of hypoglycemia and\nweight gain associated with insulin ther-apy (84,114). For individuals who ad-vance to prandial insulin, a prandial\ninsuli... | [
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0.006929066497832537,
-0.11175881326198578,
0.021326124668121338,
-0.09349069744348526,
-0.005830391775816679,
0.09125373512506485,
0.12130103260278702,
-0.048526063561439514,
0.029998663812875748,
0.061598751693964005,
0.07297726720571518,
-0.02774185873568058,
-0.0... |
insulin dose of 4 units or 10% of the\namount of basal insulin at the largestmeal or the meal with the greatestpostprandial excursion is a safe estimatefor initiating therapy. The prandial insu-\nlin plan can then be intensi fied based\non individual needs ( Fig. 9.4 ). Individu-\nals with type 2 diabetes are generally | [
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0.020996153354644775,
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0.07329227775335312,
0.1400442123413086,
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0.02709730714559555,
0.0010420492617413402,
-0.026546332985162735,
0.0107... |
als with type 2 diabetes are generally\nmore insulin resistant than those with\ntype 1 diabetes, require higher daily\ndoses ( /C241 unit/kg), and have lower\nrates of hypoglycemia (133). Titrationcan be based on home self-monitored\nblood glucose or CGM. When signi ficant\nadditions to the prandial insulin dose | [
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0.0638456717133522,
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... |
additions to the prandial insulin dose\nare made, particularly with the eveningmeal, consideration should be given to\ndecreasing basal insulin. Meta-analyses\nof trials comparing rapid-acting insulinanalogs with human regular insulin intype 2 diabetes have not reported im-\nportant differences in A1C or hypoglyce-\nmi... | [
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0.030160948634147644,
-0.02532656118273735,
0.008002860471606255,
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-0.0124... |
mia (134,135).\nConcentrated Insulins\nSeveral concentrated insulin prepara-tions are currently available. U-500 reg-\nular insulin is, by de finition, five times\nmore concentrated than U-100 regularS170 Pharmacologic Approaches to Glycemic Treatment Diabetes Care Volume 47, Supplement 1, January 2024\n©AmericanDiabetes... | [
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0.05367746204137802,
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0.07494499534368515,
0.0606708861887455,
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0.016225969418883324,
-0.0017829681746661663,
-0.08246944844722748,
-0.0253... |
1. Consider insulin as the first injectable if evidence of ongoing catabolism is present, symptoms of hyperglycemia are present, when A1C or blood glucose levels are very high (i.e., A1C >10% | [
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0.09996578842401505,
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0.002926379442214966,
0.026439819484949112,
-0.00428733928129077,
0.0583... |
[>86 mmol/mol] or blood glucose ≥300 mg/dL [≥16.7 mmol/L]), or when a diagnosis of type 1 diabetes is a possibility.2. When selecting GLP-1 RAs, consider individual preference, A1C lowering, weight-lowering effect, or frequency of injection. If CVO is present. consider GLP-1 RA with proven CVO benefit. Oral o\nr | [
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0.01353199128061533,
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0.058901067823171616,
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0.03671695664525032,
0.14620128273963928,
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-0.02939515747129917,
0.005292742047458887,
-0.07775705307722092,
0.03... |
r\n injectable GLP-1 RAs are appropriate.\n3. For people on GLP-1 RA and basal Insulin combination, consider use of a flxed-ratio combination product (IDegLira or iGlarLixi). | [
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-0.02456572651863098,
-0.14635024964809418,
-0.0002700505137909204,
-0.05361330881714821,
-0.021338006481528282,
0.09636037796735764,
0.08572133630514145,
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-0.02686709351837635,
0.04326719790697098,
-0.017915569245815277,
-0.06117726117372513,
0.0... |
4. Consider switching from evening NPH to a basal analog if the individual develops hypoglycemia and/or frequently forgets to administer NPH in the evening and would be better managed wtth an A.M. dose of a long-acting basal Insulin.5. If adding prandial insulin to NPH, consider initiation of a self-mixed or premixe... | [
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0.013410639017820358,
-0.03242715448141098,
0.06113141402602196,
-0.02763460762798786,
0.009515739046037197,
0.07243158668279648,
0.06630532443523407,
-0.043173063546419144,
0.04047609865665436,
-0.009188933297991753,
-0.003970782272517681,
-0.10073454678058624,
0.045... |
initiation of a self-mixed or premixed insulin plan to decrease the number of in jections required. | [
0.005315072368830442,
0.07985088974237442,
-0.034091100096702576,
0.06693269312381744,
-0.08981389552354813,
0.01306150946766138,
0.03931795433163643,
0.042211297899484634,
0.019460640847682953,
-0.01214541681110859,
-0.015847111120820045,
0.08361203968524933,
-0.03569218888878822,
0.02889... |
Figure 9.4 —Intensifying to injectable therapies in type 2 diabetes. DSMES, diabetes self-management education and support; FPG, fasting plasma\nglucose; GLP-1 RA, glucagon-like peptide 1 receptor agonist; dual GIP and GLP-1 RA, dual glucose-dependent insulinotropic polypeptide and glucagon- | [
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0.060481540858745575,
-0.036692988127470016,
-0.02619110979139805,
0.0579342320561409,
0.10473786294460297,
-0.023849517107009888,
-0.026479043066501617,
-0.07207450270652771,
0.07331661134958267,
-0.10440552979707718,
0.0... |
like peptide 1 receptor agonist; max, maximum; PPG, postprandial glucose. Adapted from Davies et al. (151).diabetesjournals.org/care Pharmacologic Approaches to Glycemic Treatment S171\n©AmericanDiabetesAssociation | [
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0.005922171752899885,
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0.000007553479008493014,
0.0005319881602190435,
0.11178815364837646,
-0.04107297584414482,
0.029585713520646095,
-0.015282289125025272,
0.07625079900026321,
-0.085734061896801,
0.03... |
insulin. U-500 regular insulin has distinct\npharmacokinetics with similar onset but a\ndelayed, blunted, and prolonged peak ef-\nfect and longer duration of action com-\npared with U-100 regular insulin; thus, it\nhas characteristics more like a premixed\nintermediate-acting (NPH) and regular in-\nsulin product and ca... | [
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0.0714811384677887,
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0.005779803264886141,
-0.011148571968078613,
0.05449117347598076,
-0.0678032711148262,
0.07353... |
sulin product and can be used as two or\nthree daily injections (136,137). U-300\nglargine and U-200 degludec are three\nand two times as concentrated as theirU-100 formulations, respectively, and al-\nlow higher doses of basal insulin adminis-\ntration per volume used. U-300 glargine\nhas a longer duration of action t... | [
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0.07346827536821365,
0.09744954854249954,
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-0.06086193770170212,
0.009539971128106117,
0.03851485252380371,
-0.037765201181173325,
0... |
has a longer duration of action than\nU-100 glargine but modestly lower effi -\ncacy per unit administered (138 –140).\nThe U-200 formulations of insulin deglu-\ndec, insulin lispro, and insulin lispro-aabc\nhave similar pharmacokinetics to their\nU-100 counterparts (141 –143). These | [
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0.07112466543912888,
0.12989875674247742,
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0.012565065175294876,
0.006859505083411932,
0.043715950101614,
-0.050754886120557785,
0.04528... |
U-100 counterparts (141 –143). These\nconcentrated preparations may be moreconvenient (fewer injections to achievetarget dose) and comfortable (less volume\nto inject target dose and/or less injection\neffort) for individuals and may improve\ntreatment plan engagement in those with\ninsulin resistance who require large... | [
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0.04710312932729721,
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0.05593538284301758,
0.10833542048931122,
-0.11849493533372879,
-0.03027523122727871,
0.019712576642632484,
0.013836857862770557,
0.04813022539019585,
0.081344... |
insulin resistance who require large doses\nof insulin. While U-500 regular insulin is\na v a i l a b l ei nb o t hp r e filled pens and vials,\nother concentrated insulins are avail-able only in pre filled pens to minimize | [
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0.061859164386987686,
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0.03655155375599861,
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0.08528028428554535,
0.02889888361096382,
-0.06972867995500565,
-0.018955260515213013,
-0.025179987773299217,
0.04306459426879883,
-0.0594143271446228,
0.053... |
the risk of dosing errors. If U-500Table 9.3 —Median monthly (30-day) AWP and NADAC of maximum approved daily dose of noninsulin glucose-lowering\nagents in the U.S.\nClass Compound(s)Dosage strength/\nproduct (if applicable)Median AWP\n(min, max)*Median NADAC\n(min, max)*Maximum approved\ndaily dose †\nBiguanides /C15... | [
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0.04329422116279602,
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-0.01741110347211361,
0.027893856167793274,
0.0014014366315677762,
0.03812432661652565,
0.16314294934272766,
-0.025496480986475945,
0.020572267472743988,
-0.04209643229842186,
0.03885475546121597,
-0.013638188131153584,
0.009... |
daily dose †\nBiguanides /C15Metformin 500 mg (ER)\n850 mg (IR)\n1,000 mg (IR)\n1,000 mg (ER)\n500 mg (Sol)$89 ($45, $6,719)\n$108 ($5, $189)\n$87 ($3, $144)\n$1,884 ($242, $7,214)\n$405 ($405, $739)$5\n$2$2\n$31 ($31, $226)\n$5352,000 mg2,550 mg2,000 mg\n2,000 mg\n2,000 mg\nSulfonylureas (2nd\ngeneration)/C15Glimepiri... | [
0.036037378013134,
-0.012120198458433151,
0.010911072604358196,
0.04590124264359474,
-0.0518621988594532,
-0.050849832594394684,
0.06225413456559181,
0.16144482791423798,
-0.007229708135128021,
0.0265254694968462,
-0.035947900265455246,
-0.03747126832604408,
0.015205532312393188,
-0.003311... |
generation)/C15Glimepiride\n/C15Glipizide\n/C15Glyburide4m g\n10 mg (IR)\n10 mg (XL/ER)\n6 mg (micronized)\n5m g$73 ($72, $198)\n$72 ($67, $91)\n$48 ($46, $48)\n$54 ($48, $71)\n$82 ($63, $432)$3$6\n$10$12\n$88m g\n40 mg\n20 mg\n12 mg20 mg\nThiazolidinedione /C15Pioglitazone 45 mg $348 ($7, $349) $4 45 mg\na-Glucosidase... | [
0.05019397661089897,
-0.025306163355708122,
-0.022038329392671585,
0.0522930771112442,
-0.07291749864816666,
-0.01389376726001501,
0.009428939782083035,
0.1387483924627304,
0.020876020193099976,
0.04652359336614609,
-0.002089701360091567,
0.010755239985883236,
0.015361391007900238,
0.00527... |
a-Glucosidase inhibitors /C15Acarbose\n/C15Miglitol100 mg100 mg$106 ($104, $378)$294 ($241, $346)$27\nNA300 mg300 mg\nMeglitinides /C15Nateglinide\n/C15Repaglinide120 mg\n2m g$155\n$878 ($58, $897)$27$31360 mg\n16 mg\nDPP-4 inhibitors /C15Alogliptin\n/C15Linagliptin\n/C15Saxagliptin\n/C15Sitagliptin25 mg\n5m g\n5m\ng\n... | [
0.01727047748863697,
-0.009768238291144371,
-0.008190113119781017,
0.031684547662734985,
-0.06464751809835434,
-0.01152950618416071,
-0.039862994104623795,
0.11808421462774277,
0.04034709185361862,
0.06077074632048607,
-0.02340700849890709,
0.006877273321151733,
-0.028306327760219574,
-0.0... |
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