The skepticism expressed in the article with regard to sulfonylureas is unjustified. In a recent Cochrane meta-analysis (1), second generation sulfonylureas had fewer cardiovascular side effects than metformin; mortality was the same. By comparison, the cited retrospective data provide low-level evidence. The article does not contain any concrete data on the adverse effects of sulfonylureas. Weight gain as a side effect of these drugs is clinically not relevant: 1.3 kg in 2 years (2) and 1.7 kg in 10 years (UKPDS). Hypoglycemia caused by sulfonylureas is rare: about 0.5/patient/year, for example, for glimepiride+metformin (2). These cases of hypoglycemia are mostly mild and occur in the first three months after the start of the treatment, when HbA1c values in the sulfonylurea groups drop more notably than in the comparator groups.
The authors write that treatment with DPP-4 inhibitors does not carry a risk of hypoglycemia. In combination with insulin or insulinotropic substances, however, the risk of hypoglycemia is increased by DPP-4 inhibitors, and if required the treatment has to be adjusted.
The evidence for the explained lifestyle interventions is low. An example: the lifestyle intervention in the Look AHEAD Study did not prevent cardiovascular end points.
With regard to GLP-1 analogues, no benefit has been found with regard to clinical end points. There have so far not been sufficiently large studies that really prove or exclude the risk of pancreatic cancer in patients being treated with GLP-1 analogues. The increase in spontaneous reports of pancreatic cancer cases under GLP-1 treatment remain a cause for concern. The indication for this class of substances is altogether extremely rare.
The benefits of intensified insulin treatment in patients with type 2 diabetes that the authors propose are elusive. A randomized comparison of the different forms of insulin therapy did not show any significant differences; quality of life is rather reduced under intensive treatment (3).
Footnotes
Conflict of interest statement
Prof Abholz is a member of DEGAM and was involved in developing the disease management guideline for type 2 diabetes.
Dr Egidi has received a honorarium for participating in the expert workshop of the Profil Institute, on patient relevant end points in diabetology.
Prof Müller has received honoraria for acting as an expert adviser from IQWiG and for CME events from the German Medical Association.
Prof Spranger has received consultancy fees from Bristol Myers Squibbs and Amgen. For preparing scientific CME events he has received honoraria from AstraZeneca, Bayer, BMS, MSD, Berlin-Chemie, Sanofi, and Novo. He has also received funding from Sanofi for a research project that he himself initiated.
References
- 1.Hemmingsen B, Lund SS, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013;11 doi: 10.1002/14651858.CD008143.pub3. CD008143. [DOI] [PubMed] [Google Scholar]
- 2.Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475–483. doi: 10.1016/S0140-6736(12)60691-6. [DOI] [PubMed] [Google Scholar]
- 3.Holman RR, Farmer AJ, Davies MJ, et al. 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361:1736–1747. doi: 10.1056/NEJMoa0905479. [DOI] [PubMed] [Google Scholar]
- 4.Pfeiffer AFH, Klein HH. The treatment of type 2 diabetes. Dtsch Arztebl Int. 2014;111:69–82. doi: 10.3238/arztebl.2014.0069. [DOI] [PMC free article] [PubMed] [Google Scholar]