Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy

In the paper

“Intensive glycemic management resulting in lower A1C levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes (9,10)”

What the sources say

• Not checked yetcites [9] Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes therapy and carotid intima–media thickness in type 1 diabetes. N Engl J Med 348:2294–2303, 2003 source
• Not checked yetcites [10] Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653, 2005 source

In the paper

“the increased number of choices available to practitioners and patients has heightened uncertainty regarding the most appropriate means of treating this widespread disease (14)”

What the sources say

• Not checked yetcites [14] Nathan DM: Finding new treatments for diabetes—how many, how fast . . . how good? N Engl J Med 356:437–440, 2007 source

In the paper

“Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial effect on diabetes-specific microvascular complications, including retinopathy, nephropathy, and neuropathy, in the setting of type 1 diabetes (4,5)”

What the sources say

• Not checked yetcites [4] Diabetes Control and Complications Trial Research Group: The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial. N Engl J Med 329:978–986, 1993 source
• Not checked yetcites [5] Reichard P, Nilsson B-Y, Rosenqvist U: The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 329:304–309, 1993 source

In the paper

“in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce microvascular complications (6–8)”

What the sources say

• Not checked yetcites [6] UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998 source
• Not checked yetcites [7] UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865, 1998 source
• Not checked yetcites [8] Ohkubo Y, Kishikawa H, Araki E, et al.: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with NIDDM: a randomized prospective 6-year study. Diabetes Res Clin Pract 28:103–117, 1995 source

In the paper

“Controlled clinical trials, such as the Diabetes Control and Complications Trial (DCCT) (4) and the Stockholm Diabetes Study in type 1 diabetes (5) and the UK Prospective Diabetes Study (UKPDS) (6,7) and Kumamoto study (8) in type 2 diabetes, have helped to establish the glycemic goals of therapy that result in improved long-term outcomes.”

What the sources say

• Not checked yetcites [4] Diabetes Control and Complications Trial Research Group: The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial. N Engl J Med 329:978–986, 1993 source
• Not checked yetcites [5] Reichard P, Nilsson B-Y, Rosenqvist U: The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 329:304–309, 1993 source
• Not checked yetcites [6] UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998 source
• Not checked yetcites [7] UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865, 1998 source

In the paper

“current studies have failed to demonstrate a beneficial effect of intensive diabetes therapy on CVD in type 2 diabetes (11–13)”

What the sources say

• Not checked yetcites [11] The Action to Control Cardiovascular Risk in Diabetes Study Group: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559, 2008 source
• Not checked yetcites [12] The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572, 2008 source
• Not checked yetcites [13] Abraira C, Duckworth WC, Moritz T: Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial: an interim report. Diabetes Obes Metab. 29 July 2008 [Epub ahead of print] source

In the paper

“In terms of efficacy, they appear to be similar to metformin, lowering A1C levels by ∼1.5 percentage points (26,49).”

What the sources say

• Not checked yetcites [26] Groop L: Sulfonylureas in NIDDM. Diabetes Care 15:737–747, 1992 source
• Not checked yetcites [49] DeFronzo R, Goodman A, the Multicenter Metformin Study Group: Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541–549, 1995 source

In the paper

“The most appropriate target levels for blood glucose, on a day-to-day basis, and A1C, as an index of chronic glycemia, have not been systematically studied.”

In the paper

“The glucose-lowering effectiveness of individual therapies and combinations demonstrated in clinical trials is predicated not only on the intrinsic characteristics of the intervention but also on the duration of diabetes, baseline glycemia, previous therapy, and other factors.”

In the paper

“The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which had the primary objective of decreasing CVD with interventions aimed at achieving an A1C level of <6.0% vs. interventions aimed at achieving an A1C level of <7.9%, showed excess CVD mortality in the intensive treatment group (11).”

What the sources say

• Not checked yetcites [11] The Action to Control Cardiovascular Risk in Diabetes Study Group: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559, 2008 source

In the paper

“In addition to their intention-to-treat analyses demonstrating the superiority of intensive versus conventional interventions, the DCCT and UKPDS demonstrated a strong correlation between mean A1C levels over time and the development and progression of retinopathy and nephropathy (23,24).”

What the sources say

• Not checked yetcites [23] DCCT Research Group: The association between glycemic exposure and long-term diabetic complications in the Diabetes Control and Complications Trial. Diabetes 44:968–983, 1995 source
• Not checked yetcites [24] Stratton IM, Adler AI, Neil HA, et al.: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412, 2000 source

In the paper

“However, both the DCCT (4) and the UKPDS (6,7) had as their goals the achievement of glycemic levels in the nondiabetic range.”

What the sources say

• Not checked yetcites [4] Diabetes Control and Complications Trial Research Group: The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial. N Engl J Med 329:978–986, 1993 source
• Not checked yetcites [6] UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998 source
• Not checked yetcites [7] UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865, 1998 source

In the paper

“Assiduous attention to abnormalities other than hyperglycemia that accompany type 2 diabetes, such as hypertension and dyslipidaemia, has been shown to improve microvascular and cardiovascular complications.”

What the sources say

• Not checked yetcites [1] American Diabetes Association: Standards of medical care in diabetes—2008 (Position Statement). Diabetes Care 31(Suppl. 1): S12–S54, 2008 source
• Not checked yetcites [21] Grundy SM, Cleeman JI, Merz NB, et al.: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239, 2004 source
• Not checked yetcites [22] Chobanian AV, Bakris GL, Black HR, et al.: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289:2560–2572, 2003 source

In the paper

“However, recent studies have suggested that metformin is safe unless the estimated glomerular filtration rate falls to <30 ml/min (52).”

What the sources say

• Not checked yetcites [52] Shaw JS, Wilmot RL, Kilpatrick ES: Establishing pragmatic estimated GFR thresholds to guide metformin prescribing. Diabet Med 24:1160–1163, 2007 source

In the paper

“In this setting, with a mean sustained weight loss of >20 kg, diabetes is virtually eliminated (42–45).”

What the sources say

• Not checked yetcites [42] Pories WJ, Swanson MS, MacDonald KG, et al.: Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 222:339–350, 1995 source
• Not checked yetcites [43] Sjostrom L, Lindroos AK, Peltonen M, et al.: Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 351:2683–2693, 2004 source
• Not checked yetcites [44] Dixon JB, O’Brien PE, Playfair J, et al.: Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 299:316–323, 2008 source
• Not checked yetcites [45] Pontiroli AE, Folli F, Paganelli M, et al.: Laparoscopic gastric banding prevents type 2 diabetes and arterial hypertension and induces their remission in morbid obesity: a 4-year case-controlled study. Diabetes Care 28:2703–2709, 2005 source

In the paper

“Unfortunately, the high rate of weight regain has limited the role of lifestyle interventions as an effective means of controlling glycemia in the long term.”

In the paper

“Weight loss of as little as 4 kg will often ameliorate hyperglycemia.”

In the paper

“The clinical trials, in concert with epidemiological data (18,19), support decreasing glycemia as an effective means of reducing long-term microvascular and neuropathic complications.”

What the sources say

• Not checked yetcites [18] Klein R, Klein BEK, Moss SE, et al.: Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA 260:2864–2871, 1988 source
• Not checked yetcites [19] Chase HP, Jackson WE, Hoops SL, et al.: Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA 261:1155–1160, 1989 source

In the paper

“Although the onset of the glucose-lowering effect of sulfonylurea monotherapy is relatively rapid compared with, for example, the thiazolidinediones (TZDs), maintenance of glycemic targets over time is not as good as monotherapy with a TZD or metformin (55).”

What the sources say

• Not checked yetcites [55] Kahn SE, Haffner SM, Heise MA, et al.: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443, 2006 source

In the paper

“Results from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and the Veterans Affairs Diabetes Trial, both of which had different interventions and study populations than ACCORD, did not demonstrate any excess total or CVD mortality with intensive regimens that achieved A1C levels comparable with the 6.5% in ACCORD (12,13).”

What the sources say

• Not checked yetcites [12] The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572, 2008 source
• Not checked yetcites [13] Abraira C, Duckworth WC, Moritz T: Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial: an interim report. Diabetes Obes Metab. 29 July 2008 [Epub ahead of print] source

In the paper

“Unfortunately, there is a dearth of high-quality studies that provide head-to-head comparisons of the ability of the medications to achieve the currently recommended glycemic levels.”

In the paper

“however, patients with recent-onset diabetes often respond adequately to less intensive interventions than those with longer-term disease (48).”

What the sources say

• Not checked yetcites [48] Peters AL, Davidson MB: Maximal dose glyburide in markedly symptomatic patients with type 2 diabetes: a new use for an old friend. J Clin Endocrinol Metab 81:2423, 1996 source

In the paper

“The major environmental factors that increase the risk of type 2 diabetes are overnutrition and a sedentary lifestyle, with consequent overweight and obesity (39,40).”

What the sources say

• Not checked yetcites [39] Harris MI: Epidemiologic correlates of NIDDM in Hispanics, whites and blacks in the U.S. population. Diabetes Care 14 (Suppl. 3):639–648, 1991 source
• Not checked yetcites [40] Rewers M, Hamman RF: Risk factors for non-insulin dependent diabetes. In Diabetes in America. 2nd ed. Harris M, Ed. Bethesda, MD, National Institutes of Health, 1995, p. 179–220 (NIH publ. no. 95-1468)

In the paper

“However, the different classes do have variable effectiveness in decreasing glycemic levels (Table 1)”

What the sources say

• Not checked yetcites (Table 1)

In the paper

“However, none of the studies has demonstrated a benefit of intensive glycemic control on their primary CVD outcomes.”

What the sources say

• Not checked yetcites [11] The Action to Control Cardiovascular Risk in Diabetes Study Group: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559, 2008 source
• Not checked yetcites [12] The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572, 2008 source
• Not checked yetcites [13] Abraira C, Duckworth WC, Moritz T: Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial: an interim report. Diabetes Obes Metab. 29 July 2008 [Epub ahead of print] source

In the paper

“However, the limited long-term success of lifestyle programs to maintain glycemic goals in patients with type 2 diabetes suggests that the large majority of patients will require the addition of medications over the course of their diabetes.”

In the paper

“In other words, the salutary effects of therapy on long-term complications appear to be predicated predominantly on the level of glycemic control achieved rather than on any other specific attributes of the intervention(s) used to achieve glycemic goals.”

In the paper

“Except for their differential effects on glycemia, there are insufficient data at this time to support a recommendation of one class of glucose-lowering agents, or one combination of medications, over others with regard to effects on complications.”

In the paper

“Not surprisingly, interventions that reverse or improve these factors have been demonstrated to have a beneficial effect on control of glycemia in established type 2 diabetes (41).”

What the sources say

• Not checked yetcites [41] Look AHEAD Research Group: Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the Look AHEAD trial. Diabetes Care 30:1374–83, 2007 source

In the paper

“Typically, metformin monotherapy will lower A1C levels by ∼1.5 percentage points (27,49).”

What the sources say

• Not checked yetcites [27] Bailey CJ, Turner RC: Metformin. N Engl J Med 334:574–583, 1996 source
• Not checked yetcites [49] DeFronzo R, Goodman A, the Multicenter Metformin Study Group: Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541–549, 1995 source

In the paper

“The UKPDS compared three classes of glucose-lowering medications (sulfonylurea, metformin, or insulin) but was unable to demonstrate clear superiority of any one drug over the others with regard to diabetes complications (6,7).”

What the sources say

• Not checked yetcites [6] UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998 source
• Not checked yetcites [7] UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865, 1998 source

In the paper

“Insulin therapy has beneficial effects on triacylglycerol and HDL cholesterol levels, especially in patients with poor glycemic control (74)”

What the sources say

• Not checked yetcites [74] Nathan DM, Roussell A, Godine JE: Glyburide or insulin for metabolic control in non-insulin-dependent diabetes mellitus: a randomized double-blind study. Ann Int Med 334–340, 1998 source

In the paper

“The very rapid-acting and long-acting insulin analogues have not been shown to lower A1C levels more effectively than the older, rapid-acting or intermediate-acting formulations (71–73).”

What the sources say

• Not checked yetcites [71] Horvath K, Jeitler K, Berghold A, et al.: Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2:CD005613, 2007 source
• Not checked yetcites [72] Raskin P, Allen E, Hollander P: Initiating insulin therapy in type 2 diabetes. Diabetes Care 28:260–265, 2005 source
• Not checked yetcites [73] Dailey G, Rosenstock J, Moses RG, et al.: Insulin glulisine provides improved glycemic control in patients with type 2 diabetes. Diabetes Care 27:2363–2368, 2004 source

In the paper

“Type 2 diabetes is a progressive disease (89), and patients should be informed that they are likely to require the addition of glucose-lowering medications over time.”

What the sources say

• Not checked yetcites [89] U.K. Prospective Diabetes Study Group: U.K. Prospective Diabetes Study 16: overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258, 1995 source

In the paper

“The glycemic benefits of sulfonylureas are nearly fully realized at half-maximal doses, and higher doses should generally be avoided.”

In the paper

“Thiazolidinediones (TZDs or glitazones) are peroxisome proliferator–activated receptor γ modulators; they increase the sensitivity of muscle, fat, and liver to endogenous and exogenous insulin (“insulin sensitizers”) (31).”

What the sources say

• Not checked yetcites [31] Yki-Jarvinen H: Drug therapy: thiazolidinediones. N Engl J Med 351:1106, 2004 source

In the paper

“Pioglitazone was associated with a 16% reduction in death, myocardial infarction, and stroke—a controversial secondary end point reported to have marginal statistical significance (67).”

What the sources say

• Not checked yetcites [67] Dormandy JA, Charbonnel B, Eckland DJA, et al.: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive (PROspective pioglitAzone Clinical Trial in macrovascular Events): a randomized controlled trial. Lancet 366:1279–1289, 2005 source

In the paper

“Insulin can, when used in adequate doses, decrease any level of elevated A1C to, or close to, the therapeutic goal.”

In the paper

“Nateglinide is somewhat less effective in lowering A1C than repaglinide when used as monotherapy or in combination therapy (57,58).”

What the sources say

• Not checked yetcites [57] Rosenstock J, Hassman DR, Madder RD, et al.: Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Diabetes Care 27:1265–1270, 2004 source
• Not checked yetcites [58] Gerich J, Raskin P, Jean-Louis L, et al.: PRESERVE-beta: two year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin. Diabetes Care 28:2093–2099, 2005 source

In the paper

“Several meta-analyses have suggested a 30–40% relative increase in risk for myocardial infarction (65,66) with rosiglitazone.”

What the sources say

• Not checked yetcites [65] Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356:2457–2471, 2007 source
• Not checked yetcites [66] Singh S, Loke YK, Furberg CD: Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 298:1189–1195, 2007 source

In the paper

“It is also the most effective at lowering glycemia.”

In the paper

“Oral glucose-lowering regimens that do not include sulfonylureas or glinides, and are therefore not likely to cause hypoglycemia, usually do not require SMBG (86).”

What the sources say

• Not checked yetcites [86] Farmer A, Wade A, Goyder E, et al.: Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial. BMJ 335:132, 2007 source

In the paper

“Mounting evidence suggests that aggressive lowering of glycemia, especially with insulin therapy, in newly diagnosed diabetes can result in sustained remissions, i.e., normoglycemia without need for glucose-lowering medications (87,88).”

What the sources say

• Not checked yetcites [87] Ilkova H, Glaser B, Tunckale A, et al.: Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care 20:1353–1356, 1997 source
• Not checked yetcites [88] Weng J, Li Y, Xu W, et al.: Effect of intensive insulin therapy on beta-cell function and glycemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomized parallel-group trial. Lancet 371:1753–1760, 2008 source

In the paper

“Meta-analyses have supported a possible beneficial effect of pioglitazone on CVD risk (68).”

What the sources say

• Not checked yetcites [68] Lincoff AM, Wolski K, Nicholls SJ, et al.: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 298:1180–1188, 2007 source

In the paper

“The data regarding the blood glucose–lowering effectiveness of TZDs when used as monotherapy have demonstrated a 0.5–1.4 percentage point decrease in A1C.”

In the paper

“The TZDs appear to have a more durable effect on glycemic control, particularly compared with sulfonylureas (55).”

What the sources say

• Not checked yetcites [55] Kahn SE, Haffner SM, Heise MA, et al.: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443, 2006 source

In the paper

“In clinical studies, A1C has been decreased by 0.5–0.7 percentage points (82).”

What the sources say

• Not checked yetcites [82] Riddle M, Frias J, Zhang B, et al.: Pramlintide improved glycemic control and reduced weight in patients with type 2 diabetes using basal insulin. Diabetes Care 30:2794–2799, 2007 source

In the paper

“In clinical trials, 25–45% of participants have discontinued α-glucosidase inhibitor use as a result of this side effect (29,60).”

What the sources say

• Not checked yetcites [29] Van de Laar FA, Lucassen PL, Akkermans RP, et al.: Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 2:CD003639, 2005 source
• Not checked yetcites [60] Chiasson JL, Josse RG, Gomis R, et al.: Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM Trial. JAMA 290:486–494, 2003 source

In the paper

“One clinical trial examining acarbose as a means of preventing the development of diabetes in high-risk individuals with impaired glucose tolerance showed an unexpected reduction in severe CVD outcomes (60).”

What the sources say

• Not checked yetcites [60] Chiasson JL, Josse RG, Gomis R, et al.: Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM Trial. JAMA 290:486–494, 2003 source

In the paper

“In clinical trials aimed at normoglycemia and achieving a mean A1C of ∼7%, severe hypoglycemic episodes (defined as requiring help from another person to treat) occurred at a rate of between one and three per 100 patient-years (8,75–77)”

What the sources say

• Not checked yetcites [8] Ohkubo Y, Kishikawa H, Araki E, et al.: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with NIDDM: a randomized prospective 6-year study. Diabetes Res Clin Pract 28:103–117, 1995 source
• Not checked yetcites [75] Abraira C, Johnson N, Colwell J, et al.: VA Cooperative study on glycemic control and complications in type II diabetes. Diabetes Care 18:1113–1123, 1995 source
• Not checked yetcites [76] Zammitt NN, Frier BM: Hypoglycemia in type 2 diabetes. Diabetes Care 28:2948–2961, 2005 source
• Not checked yetcites [77] Miller CD, Phillips LS, Ziemer DC, et al.: Hypoglycemia in patients with type 2 diabetes mellitus. Arch Int Med 161:1653–1659, 2005 source

In the paper

“the Prospective Pioglitazone Clinical Trial in macrovascular events (PROactive) demonstrated no significant effects of pioglitazone compared with placebo on the primary CVD outcome”

What the sources say

• Not checked yetcites [67] Dormandy JA, Charbonnel B, Eckland DJA, et al.: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive (PROspective pioglitAzone Clinical Trial in macrovascular Events): a randomized controlled trial. Lancet 366:1279–1289, 2005 source

In the paper

“Of the two glinides currently available in the U.S., repaglinide is almost as effective as metformin or the sulfonylureas, decreasing A1C levels by ∼1.5 percentage points.”

In the paper

“Concerns raised by the UGDP that sulfonylureas, as a drug class, may increase CVD mortality in type 2 diabetes were not substantiated by the UKPDS or ADVANCE study (6,12).”

What the sources say

• Not checked yetcites [6] UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998 source
• Not checked yetcites [12] The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572, 2008 source

In the paper

“Insulin plus metformin (92) is a particularly effective means of lowering glycemia while limiting weight gain.”

What the sources say

• Not checked yetcites [92] Yki-Jarvinen H, Ryysy L, Nikkila K, et al.: Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. Ann Int Med 130:389–396, 1999 source

In the paper

“However, many newly diagnosed type 2 diabetic patients will usually respond to oral medications, even if symptoms of ehyperglycemia are present (48).”

What the sources say

• Not checked yetcites [48] Peters AL, Davidson MB: Maximal dose glyburide in markedly symptomatic patients with type 2 diabetes: a new use for an old friend. J Clin Endocrinol Metab 81:2423, 1996 source

In the paper

“More than one medication will be necessary for the majority of patients over time.”